Immune Power Oil by Strauss Herb Co

POSSIBLY EFFECTIVE

• Multiple sclerosis (MS). A foreign prescription drug spray (Sativex) and oral cannabis extract seem to modestly reduce spasticity in patients with MS. It is unknown if inhaled cannabis is beneficial. Details: A meta-analysis of several clinical studies in patients with MS shows that using a specific oromucosal spray containing cannabis extract (Sativex, GW Pharmaceuticals), standardized to deliver delta-9-tetrahydrocannabinol (THC) 2.7 mg and cannabidiol (CBD) 2.5 mg per actuation, for at least 3 weeks modestly reduces subjective spasticity, but does not seem to reduce neuropathic pain or bladder dysfunction, when compared with placebo (104895). Similarly, another meta-analysis of 5 clinical studies, that includes many of the same studies as the prior meta-analysis, shows that using Sativex as add-on therapy improves the likelihood of reduced spasticity by 2.4 times when compared with placebo (113020). Limited research suggests that the benefit of Sativex might last for over 11 months and withdrawal of Sativex may cause a rebound of MS symptoms (89923,89924). Sativex has been approved in the United Kingdom as a prescription medicine to treat MS-related spasticity (89913) and in Canada to treat neuropathic pain associated with MS (61775). This product has not been approved in the United States. The American Academy of Neurology states that Sativex does not improve objective measures of spasticity, reduce the number of urinary incontinence episodes, or reduce MS-related tremors (89460). Notably, much of the research was funded by the manufacturer. Oral cannabis extracts have also been studied. A meta-analysis of clinical research in patients with MS shows that taking a cannabis extract containing THC 25-30 mg and CBD 8-18 mg daily for up to 15 weeks modestly reduces subjective spasticity, neuropathic pain, and bladder dysfunction when compared with placebo. However, objective spasticity measures (Ashworth scale) were not improved when compared with placebo (104895). Two of the largest studies included in the meta-analysis used a specific cannabis extract (Cannador, Society for Clinical Research) (11168,91919). A third study used cannabis extract standardized to THC 2.5 mg and CBD 0.9 mg per capsule, for an escalating daily dose of 6-12 capsules in 3 divided doses (61746). One small clinical study in patients with MS with upper limb tremors shows that taking a specific cannabis extract (Cannador) titrated to a maximum of THC 0.125 mg/kg twice daily for 2 weeks does not appear to improve tremor when compared with placebo (61739). It is unclear if SMOKING cannabis improves MS symptoms. Epidemiological research suggests that smoking cannabis is associated with reduced muscle spasms, pain in the extremities, and tremors associated with MS (11167). Recent clinical practice guidelines for the use of cannabis and cannabinoid-based medicines for the management of chronic pain strongly recommend the use of cannabinoid-based medicines as adjunct treatment for improvement of pain, muscle spasm, and sleep in patients with MS and inadequate response to other treatments. These recommendations are based on low or moderate quality evidence of smoked cannabis, cannabis extract, and oromucosal THC, suggesting that benefits exceed the risks of non-serious adverse effects. The strongest evidence of benefit has been shown with oils and capsules, as opposed to smoking or oromucosal formulations. A total daily dose of THC 10-15 mg was most commonly used in clinical research. Initiating treatment with a low dose reduces the risk of adverse effects (110321).
• Neuropathic pain. Inhaled cannabis seems to temporarily reduce neuropathic pain in some patients, although the optimal dose remains unclear. Details: A meta-analysis of five small clinical studies shows that inhaling cannabis providing delta-9-tetrahydrocannabinol (THC) in doses of approximately 1.6-96 mg daily for up to 2 weeks reduces the intensity of neuropathic pain caused by HIV, trauma, diabetes, chemotherapy, and other conditions (96383). Six patients with chronic neuropathic pain would need to inhale THC-containing cannabis for one patient to experience a pain reduction of at least 30% (96383). A small clinical trial also shows that inhaling cannabis containing 2.9% or 6.7% THC reduces neuropathic pain due to spinal cord injury. About 3 patients would need to inhale cannabis during an 8-hour period for one person to achieve a pain reduction of at least 30%. Pain relief was immediate, but lasted less than 2 hours (96379). Cannabis has been smoked, vaporized, or inhaled from gelatin capsules in a pipe (17371,61800,61833,61846,96383,96388,96379). There is speculation that smoking cannabis may relieve chronic neuropathic pain similar to gabapentin, but high-quality research is needed to confirm (96383).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. It is unclear if smoked cannabis with a high concentration of cannabidiol is beneficial for reducing alcohol use in patients with alcohol use disorder. Details: Observational research in people with alcohol use disorder suggests that smoking 1-3 grams of cannabis flower containing about 24% cannabidiol (CBD) and 1% delta-9-tetrahydrocannabinol (THC) over 5 days is associated with reduced alcohol use when compared with smoking cannabis with equal parts CBD (10%) and THC (9%) or higher THC (24%) than CBD (1%) (105496). This study is limited by its observational nature and short duration.
• Alzheimer disease. It is unclear if sublingual cannabis improves behavior in patients with Alzheimer disease. Details: Preliminary clinical research in patients with Alzheimer disease shows that taking sublingual cannabis extract (Bedrocan, Bedrocan International BV, Veendam, The Netherlands) 0.5 to 1 mL twice daily for 12 weeks modestly improves appetite, mood, and behavior, including aggression, when compared to baseline. There were also some modest improvements in some, but not all, cognitive outcomes. The cannabis extract contained 0.5% cannabidiol and 22% delta-9-tetrahydrocannabinol (111085). This study is limited by its small size and lack of control treatment.
• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). It is unclear if smoking cannabis improves symptoms of ALS. Details: Population research in patients with ALS has found that smoking cannabis is associated with improved appetite and reduced depression, pain, spasms, and drooling (61737).
• Anxiety. It is unclear if non-inhaled cannabis is beneficial for anxiety. Details: A review of five clinical studies in adults with cancer shows that non-inhaled medical cannabis does not reduce the severity of anxiety symptoms when compared with control (115355).
• Blepharospasm. It is unclear if oral cannabis extract is beneficial for blepharospasm previously unresponsive to botulism toxin injections. Details: A very small clinical trial in adults with blepharospasm unsuccessfully treated with botulism toxin A injections shows that using a cannabis extract containing delta-9-tetrahydrocannabinol (THC) 3.2% (1 drop estimated to contain 1.2 mg), titrated to a maximum of 10 drops, nightly for 12 weeks improves the frequency, duration, and severity of eyelid spasm attacks when compared with placebo (108691). The validity of this study is limited by poor study design and lack of follow-up.
• Cachexia. It is unclear if oral cannabis extract improves appetite in patients with cancer-related anorexia-cachexia syndrome. Details: One clinical study shows that using a cannabis extract standardized to contain delta-9-tetrahydrocannabinol (THC) 2.5 mg and cannabidiol (CBD) 1 mg twice daily for 6 weeks does not increase appetite when compared with placebo in patients with cancer-related anorexia-cachexia syndrome (61785). However, the substantial placebo effect and dropout rate limits the reliability of these findings.
• Cancer-related anorexia. It is unclear if non-inhaled cannabis is beneficial for cancer-related anorexia. Details: A meta-analysis of 3 clinical studies in adults with cancer shows that non-inhaled medical cannabis increases the odds of improved self-reported appetite and reduces the severity of appetite loss when compared with control (115355).
• Cancer-related pain. It is unclear if oral or inhaled cannabis products are beneficial for patients with cancer-related pain. The evidence is mixed. Details: Clinical practice guidelines from the American Society of Clinical Oncology conclude that evidence is insufficient to recommend for or against the use of cannabis to manage cancer-related pain (115047). Conversely, a 2021 British Medical Journal clinical practice guideline states that the evidence weakly supports a trial of non-inhaled medical cannabis in conjunction with standard pain management in individuals with moderate to severe chronic pain and insufficient pain relief. The recommendation is based on research in studies using non-inhaled medical cannabis products containing delta-9-tetrahydrocannabinol (THC) or cannabidiol (CBD) for 1-4 months showing modest improvements in pain, physical function, and sleep, but not emotional, role, or social functions, when compared with standard treatment alone (108676,108698). However, the recommendations suggest using products providing specific doses of THC and CBD and do not recommend inhaled cannabis or other oral cannabis products (108698). For more information on the specific doses of THC and CBD, see the individual monographs for these cannabinoids. A specific oromucosal cannabis extract spray (Sativex, GW Pharmaceuticals), standardized to deliver delta-9-tetrahydrocannabinol (THC) 2.7 mg and cannabidiol (CBD) 2.5 mg per actuation, has also been evaluated. Meta-analyses of up to 5 clinical studies in patients with chronic, cancer-related pain receiving prescription opioids show that using this spray for 2-5 weeks does not improve prescribed opioid consumption, sleep, or pain. One meta-analysis shows that taking this spray actually increases nausea and vomiting by 43% and 50%, respectively, when compared with opioids alone (108676,111095). All studies instructed patients not to alter the prescribed opioid dose, which may have increased the risk for adverse effects such as nausea and vomiting.
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if oral cannabis or an oromucosal cannabis extract spray are beneficial for the prevention of CINV. Details: Clinical practice guidelines from the American Society of Clinical Oncology weakly recommend that adults who are experiencing refractory CINV despite the use of recommended antiemetic prophylaxis may consider adding a prescription cannabinoid, such as nabilone or dronabinol, or a quality-controlled oral extract providing equal parts delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), to their antiemetic regimen (115047). A small clinical study in adults receiving moderately-to-highly emetogenic chemotherapy who are still experiencing CINV despite conventional antiemetic prophylaxis shows that taking a cannabis extract (TN-TC11M) containing THC 2.5 mg and CBD 2.5 mg 3 times daily during chemotherapy days 1-5 prevents CINV in 25% of patients, compared with 14% of patients receiving usual care. This means that 9 patients must be treated with cannabis in order to prevent CINV in one person (104489). Limited research has also evaluated a specific cannabis extract oromucosal spray (Sativex, GW Pharmaceuticals) standardized to deliver THC 2.7 mg and CBD 2.5 mg per actuation. A very small clinical study shows that when used in addition to a standard antiemetic regimen, 1-3 sprays after each daily chemotherapy infusion and then up to 8 sprays every 4 hours as needed for 4 days, prevents delayed CINV in 71% of patients, compared with only 22% of patients in the placebo group. There was no between-group difference in the occurrence of acute CINV, which was low in both groups (96814). This study is limited due to its small size and non-standardized treatment regimens.
• Cognitive function. It is unclear if medical cannabis is beneficial for cognitive function. Details: A small observational study in adults suggests that using medical cannabis containing low amounts of THC (64-36 mg/week) and high amounts of CBD (202-114 mg/week) to treat various conditions for 12 months may be associated with modest improvement in some measures of executive function, but no changes in memory or cognitive performance, when compared to baseline (108681). However, this study may have been too short to identify effects on cognition. In addition, improvement of clinical symptoms (e.g., pain or sleep) may correlate with cognitive improvement; results may not apply to patients using cannabis for recreational reasons.
• Crohn disease. It is unclear if oral cannabis oil or smoked cigarettes containing cannabis flowers can improve Crohn disease symptoms. Details: A small clinical study in patients with mild to moderate Crohn disease shows that using a cannabis oil containing delta-9-tetrahydrocannabinol (THC) 4% and cannabidiol (CBD) 16%, titrated gradually to satisfactory response to a maximum of 20 drops (THC 40 mg) twice daily before meals for 8 weeks, in conjunction with standard care such as corticosteroids, improves patient satisfaction and some symptoms such as abdominal pain and number of daily bowel movements, but does not improve disease activity scores or endoscopic findings, when compared with placebo (108678). Another very small clinical study shows that smoking cigarettes containing cannabis flowers 0.5 grams standardized to THC 115 mg twice daily for 8 weeks does not improve Crohn disease remission rates when compared with placebo cigarettes. However, the response rate, defined as a reduction in Crohn Disease Activity Index score of at least 100 points, was 90% in the cannabis group, compared with 40% in the placebo group. Quality of life was also improved (96387).
• Depression. It is unclear if non-inhaled cannabis is beneficial for depression. Details: A review of five clinical studies in adults with cancer shows that non-inhaled medical cannabis does not reduce the severity of depression symptoms when compared with control (115355).
• Fibromyalgia. It is unclear if inhaled cannabis vapor might reduce fibromyalgia pain. Details: A small clinical study in female adults with fibromyalgia and chronic pain shows that a single vapor inhalation of cannabis containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) increases the pressure pain threshold. Inhaling cannabis containing THC 22.4 mg and less than 1 mg of CBD also reduces pain scores by 30% when compared with placebo. However, inhaling cannabis containing THC 13.4 mg and CBD 17.8 mg does not improve pain when compared with placebo. Additionally, no cannabis products affected electrical pain thresholds or spontaneous pain scores (101420). Recent clinical practice guidelines for the use of cannabis and cannabinoid-based medicines for the management of chronic pain strongly recommend the use of cannabinoid-based medicines as adjunct treatment for improvement of chronic back, fibromyalgia, or other pain in patients with fibromyalgia and inadequate response to other treatments. These recommendations are based on low quality evidence suggesting that benefits exceed the risks of non-serious adverse effects. Initiating treatment with a low dose reduces the risk of adverse effects (110321).
• Glaucoma. It is unclear if smoking cannabis affects glaucoma risk or severity. Details: Smoking seems to reduce intraocular pressure in patients with glaucoma. However, the effect is short-term (1268). There is some evidence that cannabis can decrease blood flow to the optic nerve (1268). Decreased ocular blood flow has been associated with increased visual field loss in patients with glaucoma (92664). So far, it is not known if smoking cannabis can improve visual function (1268).
• HIV/AIDS-related wasting. It is unclear if oral or smoked cannabis might attenuate wasting in patients with HIV. Details: A questionnaire-based study has found that up to 97% of patients with HIV who smoke or ingest cannabis to treat symptoms experience improvements in appetite (61753). However, it is unclear if there are specific beneficial effects on wasting and controlled clinical research is needed to confirm these results. Recent clinical practice guidelines for the use of cannabis and cannabinoid-based medicines for the management of chronic pain strongly recommend the use of cannabinoid-based medicines for management of nausea, lack of appetite, and weight loss in patients with HIV also using antiretroviral therapies (110321).
• Hypertension. It is unclear if oral cannabis oil lowers blood pressure. Details: A very small study in older adults with hypertension shows that taking cannabis oil containing 1% to 10% delta-9-tetrahydrocannabinol (THC) and 2% to 20% cannabidiol (CBD), for an average total daily dose of about 21 mg of each cannabinoid, seems to modestly reduce blood pressure when compared with baseline (104480). The validity of this finding is limited by the lack of a control group and the non-standardized formulations and dosing used.
• Migraine headache. It is unclear if inhaled cannabis reduces migraine severity. Details: Observational research in adults with migraine found that self-reported cannabis use via inhalation (smoking, vaping, etc.) is associated with a subjective reduction in migraine symptom severity. However, females were more likely than males to report a worsening in severity after cannabis use. Additionally, cannabis users reported a reduced magnitude of effect over time and an increase in the cannabis dose used, suggesting the development of tolerance (101487). Recent clinical practice guidelines for the use of cannabis and cannabinoid-based medicines for the management of chronic pain weakly recommend the use of cannabinoid-based medicines as adjunct treatment for management of chronic headaches, including migraines and inadequate response to other treatments. These recommendations are based on low quality evidence related to cannabis suggesting that benefits exceed the risks of non-serious adverse effects. Initiating treatment with a low dose reduces the risk of adverse effects. The administration route may be patient specific (110321).
• Obsessive-compulsive disorder (OCD). Although there is interest in using cannabis for OCD, there is insufficient reliable information about the clinical effects of cannabis for this condition.
• Pain (chronic). It is unclear if most oral or inhaled cannabis products are beneficial for patients with chronic pain. Some medical non-inhaled cannabis products seem to be beneficial in patients with chronic pain due to various causes. Details: A 2021 British Medical Journal clinical practice guideline states that the evidence weakly supports a trial of non-inhaled medical cannabis in conjunction with standard pain management in individuals with moderate to severe chronic pain and insufficient pain relief. The recommendation is based on research in studies using non-inhaled medical cannabis products containing delta-9 tetrahydrocannabinol (THC) or cannabidiol (CBD) for 1-4 months showing modest improvements in pain, physical function, and sleep, but not emotional, role, or social functions, when compared with standard treatment alone (108676,108698). Recent clinical practice guidelines for the use of cannabis and cannabinoid-based medicines for the management of chronic pain strongly recommend the use of cannabinoid-based medicines, especially THC-predominant formulations, alone and/or as adjunct treatment for improvement of anxiety, pain, and sleep, in individuals with chronic pain not responsive to, or intolerant of, non-pharmacologic treatment. This recommendation includes slowly introducing cannabinoid-based medicines for individuals experiencing unsatisfactory response from, using high doses of, or experiencing adverse effects related to, opioids. These guidelines also weakly recommend the adjunct use of cannabinoid-based medicines for improvement of depression, mobility, nausea, and post-traumatic stress disorder (PTSD) in patients with chronic pain, stating that the risk of non-serious adverse events outweighs the risk of adverse events associated with standard analgesics. These recommendations are based on studies investigating a variety of cannabinoid-based medicines, including oral or inhaled whole plant, extracts, and isolated cannabinoids. The use of non-inhaled products, and/or initiating treatment with a low dose and titrating as needed, reduces the risk of adverse effects (110321). Specific doses of THC and CBD, and not other oral or inhaled cannabis products, may be recommended for some outcomes (108698,110321). For more information on the specific doses of THC and CBD, see the individual monographs on these cannabinoids. However, not all professional organizations agree. A Presidential Task Force from the International Association for the Study of Pain (IASP) does not endorse the use of cannabis or cannabinoids for pain relief due to the lack of high-quality evidence and significant gaps in scientific knowledge (115380). A meta-analysis of low- to moderate-quality clinical studies in adults with chronic non-cancer pain shows that using non-inhaled medical cannabis for 1-6 months improves pain, physical functioning, and sleep quality, but not role, social or emotional functioning, when compared with placebo. Additionally, a meta-analysis of other low- to moderate-quality clinical studies shows that there may be little to no difference between cannabis and opioids for improving pain, physical functioning, and sleep quality. However, opioids were associated with a higher odds of discontinuation due to adverse events (115045). The effects of a specific inhaled cannabis product have also been investigated. A small clinical study in patients with chronic pain shows that a single inhalation of a cannabis extract containing THC 0.5 mg or 1 mg reduces pain for 150 minutes when compared with baseline. However, only the THC 1 mg dose reduces pain when compared with placebo (104481). Due to the single-dose nature of this study, the effects of continued administration of inhaled cannabis containing THC on chronic pain are unclear. Also, the effect of most oral or inhaled cannabis products in patients with chronic pain is unclear. The placebo response in the available research is moderate to large and any additional benefit of cannabis-based products is small and possibly insignificant (110230).
• Parkinson disease. It is unclear if smoking cannabis or taking oral cannabis extract is beneficial for improving Parkinson disease symptoms. Details: An observational study in patients with Parkinson disease has found that smoking cannabis 0.5 grams during a single session improves most motor symptoms, including tremor, rigidity, and bradykinesia, by 30 minutes after smoking. Patient-reported pain and quality of sleep also improved (96813). Most preliminary clinical research included in a meta-analysis shows that cannabis, usually inhaled, improves specific symptoms such as pain, sleep problems, anxiety and rigidity (108685). However, a small clinical trial in patients with Parkinson disease shows that using a specific cannabis extract standardized to THC 2.5 mg and cannabidiol 0.8-1.8 mg per capsule (Cannador, Society for Clinical Research) twice daily for 4 weeks does not improve the severity of disease when compared with placebo. Dosing was escalated over the 4-week period reaching THC levels of 0.034 to 0.25 mg/kg daily (108342).
• Post-traumatic stress disorder (PTSD). It is unclear if smoking cannabis is beneficial for PTSD. Details: A small clinical crossover study in veterans with PTSD shows that self-administration of smoked cannabis, titrated to a maximum dose of 1.8 grams daily for 3 weeks, improves PTSD symptoms when compared with baseline, but not when compared with placebo. Patients used cannabis flower that contained either delta-9-tetrahydrocannabinol (THC) 12%, cannabidiol (CBD) 11%, or a combination of THC 7.9% with CBD 8.1% (108675). The validity of this finding is limited due to unclear reporting.
• Rheumatoid arthritis (RA). It is unclear whether an oromucosal cannabis spray (Sativex) improves RA symptoms. Details: A small clinical study in adults with RA shows that using a specific oromucosal cannabis spray (Sativex, GW Pharmaceuticals), containing delta-9-tetrahydrocannabinol (THC) 2.7 mg and cannabidiol (CBD) 2.5 mg per actuation, daily for 5 weeks may help decrease morning pain and improve quality of sleep, but not joint stiffness or total pain intensity, when compared with placebo (61762).
• Sickle cell disease. It is unclear if vaporized cannabis is beneficial for reducing chronic pain associated with sickle cell disease. Details: A small clinical study in patients with sickle cell disease and chronic pain shows that inhaling vaporized cannabis, containing 4.4% delta-9-tetrahydrocannabinol (THC) and 4.9% cannabidiol (CBD), 3 times daily for 5 days does not seem to reduce pain ratings or opioid use when compared with placebo cannabis containing no active cannabinoids (104479). This study is limited by its short duration and small sample size.
• Stress. It is unclear if cannabis is beneficial for reducing cancer-related stress. Details: A review of two clinical studies in adults living with cancer shows that using medical cannabis does not reduce stress when compared with control (115355).
• Substance use disorder. It is unclear if cannabis use is associated with non-medical opioid use in adults receiving pharmacological treatment for opioid use disorder. Details: A meta-analysis of 10 longitudinal studies in adults receiving methadone, buprenorphine, or naltrexone for opioid use disorder for an average of 10 months found that cannabis use is not associated with the risk of non-medical opioid use when compared with no cannabis use (115364).
• Ulcerative colitis. Small studies suggest that smoking cannabis flower may improve symptoms of ulcerative colitis; however, it is unclear if cannabis improves clinical response. Details: A small clinical trial in patients with mild to moderately active ulcerative colitis shows that smoking a cannabis flower cigarette containing delta-9-tetrahydrocannabinol (THC) 80 mg twice daily for 8 weeks, in conjunction with standard therapy, improves Lichtiger disease activity index scores, abdominal pain, and number of bowel movements, but does not improve endoscopic disease activity or markers of inflammation, when compared with placebo. At a 1-year follow-up, all patients who received cannabis and achieved remission during the study retained long-term remission (108680). Observational research in hospitalized adults with ulcerative colitis has found that cannabis use (undetermined route of administration) is linked with a lower rate of partial or total colectomy and a lower prevalence of bowel obstruction when compared with no cannabis use (101422). More evidence is needed to rate cannabis for these uses.

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POSSIBLY SAFE ...when a specific cannabis extract spray (Sativex, GW Pharmaceuticals) is applied topically into the oral mucosa for up to 2 years. This product is available as a prescription drug in the UK and Canada; it is an investigational new drug in the US (61775,61820,89460,89913,111095). POSSIBLY UNSAFE ...when used orally or inhaled in large amounts or for an extended duration. Edible cannabis products containing at least 50 mg of delta-9-tetrahydrocannabinol (THC) have been associated with cases of anxiety, psychosis, myocardial infarction, and ventricular arrhythmia (103796). Smoking or vaping cannabis can cause various respiratory problems such as coughing, wheezing, and inflammation of the upper respiratory tract, and is associated with increased risk of myocardial infarction and stroke (96378,99581,101420,113092,115363). E-cigarette, or vaping, product-use associated lung injury (EVALI) has occurred among adults and children who use e-cigarette, or vaping, products. The majority of patients with EVALI reported using THC-containing products, such as cannabis, in the 3 months prior to the development of symptoms (101421). Although it is possible that other ingredients, such as vitamin E acetate, may be involved in these cases of lung injury, the US Food and Drug Administration (FDA) has warned the public to stop using all THC-containing vaping products due to the risk for EVALI (101429). Cannabis use has also been associated with seizures, cognitive impairment, and mood disturbances. Cessation of cannabis may precipitate cannabis withdrawal syndrome in up to 47% of regular users, the severity of which depends on the frequency and quantity of cannabis use prior to cessation (61896,91909,96378,96381,99588,99576,99580,102801). Excessive and prolonged cannabis use, either by smoking and/or oral use, can lead to cannabinoid hyperemesis syndrome (CHS). This condition is characterized by severe, repeat bouts of nausea and vomiting that cannot be alleviated by conventional antiemetics (99585,99577). In several cases, CHS has been linked to severe complications resulting in death (99585). There is insufficient reliable information available about the safety of cannabis when used orally or via inhalation, short-term and in moderate amounts.

PREGNANCY: UNSAFE
when used orally or inhaled. Constituents in cannabis pass through the placenta and can reduce fetal growth and increase the risk for preterm birth (101425,101481,103792,104490). Cannabis use during pregnancy is also associated with placental abruption, stillbirth, preterm delivery, fetal abnormalities, congenital birth defects of various organ systems, low birth weight, small for gestational age, increased need for neonatal intensive care, and childhood leukemia (4260,25162,61855,96380,101425,101481,101483,108699,113018,115358). Prenatal cannabis use has also been associated with long-term adverse developmental effects in the offspring, such as worsened cognition, increased risk for neurodevelopmental disorders such as autism spectrum disorder and attention deficit hyperactivity disorder, and increased risk for psychological issues during adolescence (103792,104485,115356). Due to the observational nature of these studies, it is unclear if cannabis causes these adverse effects. Umbilical artery Doppler scans also show that cannabis use can increase placental vascular resistance (101483). Cannabis use during pregnancy has been associated with increased risk of anemia and hypertension in the mother (96380,101481). The rate of negative fetal outcomes due to cannabis use during pregnancy may have been previously underestimated due to reliance on maternal self-reporting of use. Recent programs requiring maternal urine toxicology testing have increased awareness of maternal cannabis use and suggest that negative fetal outcomes occur more frequently than previously recorded (101481,101482).

LACTATION: LIKELY UNSAFE
when used orally or inhaled. Delta-9-tetrahydrocannabinol (THC) is concentrated and excreted in breast milk for longer than 6 weeks after cessation of cannabis use (2619,2620,104894); prolonged cannabis use during lactation has been associated with delayed motor development (25163). Observational research in mothers who successfully abstained from cannabis use for 6 weeks (confirmed by a negative THC urine screen) after smoking cannabis prenatally at least twice weekly, found that THC levels in breastmilk increased during the first 2 weeks of abstinence and then decreased but remained detectable at 6 weeks (104894). For patients planning to breastfeed, recommend abstaining from cannabis use prenatally and during lactation. Recommendations to discard breastmilk until THC levels are undetectable are not practical, as this may take more than 6 weeks.

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ALCOHOL (Ethanol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cannabis might have additive effects when used with alcohol.  Details Cannabis can have CNS depressant effects, similar to synthetic delta-9-tetrahydrocannabinol (THC). Theoretically, concomitant use of alcohol with cannabis can have additive effects including psychomotor impairment, sedation, and changes in mood and behavior (2619).

ANESTHESIA Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Cannabis use might alter the safety and clinical effects of various forms of anesthesia.  Details A small clinical study shows that higher doses of propofol may be needed to achieve relaxation and loss of consciousness in chronic cannabis users compared with nonusers (96378). Another small clinical study shows that use of cannabis within 72 hours prior to undergoing surgery requiring atropine anesthesia may increase the risk of sustained postoperative tachycardia (95727). The exact mechanisms of these interactions are unclear. Obtain a patient's history of cannabis use preoperatively and advise patients to discontinue cannabis use for at least 2 weeks prior to undergoing surgery.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, cannabis might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs.  Details In vitro research shows that the cannabis constituents delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) inhibit platelet aggregation (61689,61917).

ANTIPSYCHOTIC DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Unlikely •  Level of Evidence = B Cannabis does not seem to affect blood levels or effects of some antipsychotic drugs.  Details Human research shows that cannabis use does not affect blood levels or clinical effects of amisulpride, aripiprazole, or olanzapine in patients with schizophrenia and related disorders (111075).

BARBITURATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, cannabis might increase the levels and adverse effects of barbiturates.  Details Some research shows that synthetic delta-9-tetrahydrocannabinol (THC) increases the elimination half-life of pentobarbital by 4 hours when dosed concomitantly (16815).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, cannabis might have additive effects if used with other CNS depressants.  Details Cannabis can have CNS depressant effects. Combining cannabis with other CNS depressants might result in additive or synergistic effects (16815,61934). A small clinical trial in healthy adults shows that inhaling a high-grade cannabis (Bedrocan International B.V., Veendam, The Netherlands) 100 mg, containing delta-9-tetrahydrocannabinol 21.8% and cannabinol 0.1%, modestly increases subjective feelings of sedation when compared with cannabis alone (111096).

CYTOCHROME P450 2C9 (CYP2C9) INDUCERS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, drugs that are CYP2C9 inducers might decrease the effects of cannabis.  Details Delta-9-tetrahydrocannabinol (THC), an active constituent of cannabis, is a substrate of CYP2C9 enzymes (99747).

CYTOCHROME P450 2C9 (CYP2C9) INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, drugs that are CYP2C9 inhibitors might increase the adverse effects of cannabis.  Details Delta-9-tetrahydrocannabinol (THC), an active constituent of cannabis, is a substrate of CYP2C9 enzymes (99747).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cannabis might increase the levels and adverse effects of CYP2C9 substrates.  Details In vitro research shows that the cannabis constituents delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol moderately inhibit the CYP2C9-mediated 7-hydroxylation of S-warfarin in a concentration-dependent manner (99578). In vitro research also shows that cannabis extracts modestly inhibit the CYP2C9 metabolism of tolbutamide; extracts providing the specific cannabinoids CBD and cannabigerol (CBG) had stronger inhibitory effects than extracts containing THC and CBD (111098).

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cannabis might decrease the levels and clinical effects of CYP2E1 substrates.  Details In vitro research shows that cannabis can induce the activity of CYP2E1, which might increase the metabolism of CYP2E1 substrates (61726).

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, CYP3A4 inducers might reduce the levels and clinical effects of cannabis.  Details Delta-9-tetrahydrocannabinol (THC), an active constituent of cannabis, is a substrate of CYP3A4 enzymes (99747).

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of cannabis.  Details Delta-9-tetrahydrocannabinol (THC), an active constituent of cannabis, is a substrate of CYP3A4 enzymes (99747).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cannabis may increase the levels and adverse effects of CYP3A4 substrates.  Details In vitro research shows that cannabis can inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates (25160). In vitro research also shows that cannabis extracts modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids CBD and cannabigerol (CBG) had stronger inhibitory effects than extracts containing THC and CBD (111098).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, cannabis might alter levels of drugs that are substrates of P-glycoprotein (P-gp).  Details Most in vitro research suggests that constituents of cannabis, including cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), can inhibit P-gp and increase the accumulation of probe compounds by reducing P-gp mediated drug efflux. In vitro studies in kidney cell lines show that a 1-hour exposure to CBD and THC inhibits P-gp (61769,104889). Cannabis may also alter the expression of P-gp, although this effect appears to vary based on duration of exposure. Some in vitro research in lymphoblastoid leukemia cell lines indicates that a 1-hour exposure to cannabinoids does not affect P-gp expression, while a prolonged 72-hour exposure decreases P-gp expression (61771). Other in vitro research in these cell lines shows that a 4-hour exposure to THC and CBD induces P-gp gene expression, while exposure for longer than 4 hours and up to 48 hours does not induce P-gp gene expression (104893).

THEOPHYLLINE Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Smoking cannabis while taking theophylline might reduce the levels and clinical effects of theophylline.  Details Similar to smoking tobacco, smoking cannabis seems to increase the metabolism of theophylline (16815).

THROMBOLYTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Cannabis might augment the effects of thrombolytic drugs and increase the risk of severe bleeding.  Details A case of cerebral hemorrhage has been reported for a 51-year-old female and chronic cannabis user who had consumed a large amount of cannabis prior to receiving recombinant tissue plasminogen activator (rtPA) for ischemic stroke. Hemorrhage had been ruled out prior to providing the rtPA. The exact mechanism of this interaction is unclear (96799).

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Concomitant use with cannabis seems to increase the levels and clinical effects of warfarin.  Details In vitro research shows that the cannabis constituents delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol inhibit the cytochrome P450 2C9 (CYP2C9)-mediated 7-hydroxylation of S-warfarin in a concentration-dependent manner. There are also three case reports of patients chronically taking warfarin that developed a spike in international normalized ratio (INR) after smoking cannabis or taking medical cannabis orally. One of the patients smoked 2-2.5 grams in one week and another patient had doubled the amount of THC consumed from 7.5 mg to 14.7 mg daily for one week. The dose smoked by the third patient is unknown (16832,99578,104483).

(Read more about CANNABIS)

General ...When inhaled or used orally, cannabis can cause various adverse effects. A specific oromucosal spray containing cannabis extract (Sativex) seems to be well tolerated when used appropriately.
Most Common Adverse Effects:
All ROAs: Dizziness, dry mouth, fatigue, headache, increased appetite, nausea, paranoid and dissociative thinking, and sedation. Intoxicating doses can impair declarative memory, motor coordination, reaction time, and visual perceptions for up to 8 hours.
Inhaled: Upper respiratory tract symptoms, such as cough and wheeze.
Serious Adverse Effects (Rare):
All ROAs: Higher doses of cannabis might cause acute coronary syndrome, arrhythmias, myocarditis, blood pressure changes, cannabinoid hyperemesis syndrome (CHS), hallucinations, pancreatitis, panic, psychosis, and seizures.
Inhaled: Upper respiratory tract symptoms, such as acute eosinophilic pneumonia and drug-induced lung injury. Smoking cannabis daily is associated with increased risk of myocardial infarction and stroke.

Cardiovascular ...Orally, edible cannabis products reported to contain 50 mg or more of delta-9-tetrahydrocannabinol (THC) have been associated with myocardial infarction (MI) and ventricular arrhythmia (103796). An epidemiological study in adults 18-74 years old suggests daily cannabis use is associated with a 25% increased odds of MI when compared with non-use, with lower odds for less than daily use, regardless of prior history of cigarette or e-cigarette use (113092). However, cannabis was smoked by 74% of respondents; it is unclear if this association applies to other routes of administration. A case-control study suggests that there is a 4.8-fold increased risk of MI within the first hour after smoking cannabis (91909). Also, there are cases of MI that have occurred soon after smoking cannabis, although this was reported to be triggered by physical activity in some regular cannabis users (61840,96378,104491,111073,111074). In many of these reports, it is unclear if the events were associated with cannabis use or other cardiovascular risk factors such as tobacco use and/or overweight (108692). However, there is at least one case following cannabis use that did not have any other notable cardiovascular risk factors. This 16-year-old healthy male presented with chest pain and an acute MI after smoking cannabis and drinking alcohol (99588). In another case, a 31-year-old male, who was a regular user of cannabis and had a previously undiagnosed myocardial bridge, presented with an MI (111073). In another case, a previously healthy 36-year-old male with a long-term history of cannabis use presented with a suspected spontaneous coronary artery dissection that resulted in cardiac arrest and cardiac catheterization (112924).
Cannabis has also been associated with acute coronary syndrome (ACS) (91920,96378,104491,108688). In some cases, the causality is unclear because patients had other risk factors such as overweight, obesity, and/or tobacco use (91920). In other cases, acute coronary events occurred in young males with no other risk factors for cardiovascular disease besides smoking (96378,108688). In one case report, ACS was linked to severe complications resulting in sudden cardiac death in a younger adult male with no past medical history (108688). Furthermore, in adults with existing coronary artery disease, the regular use of cannabis has been associated with ACS after physical activity (96378).
Over 30 case reports suggest a causal relationship between cannabis use and ischemic stroke occurrence and/or recurrence (91913,91915,96378,108694). However, despite this temporal association, evidence from prospective studies is needed to support the link. In many of the reported cases, the patients also regularly consumed alcohol and tobacco, which could have been additional contributing factors (91913,91915). Other drugs of abuse may have also contributed. One epidemiological study in adults 18-44 years of age who were abusing multiple substances, mainly amphetamines and cocaine, suggests that the addition of cannabis use is associated with 76% higher odds of ischemic stroke (92665). Some studies also suggest that cannabis independently increases stroke risk. An epidemiologic study in young adults suggests that cannabis use within the last 30 days is associated with an 82% increased odds of stroke. The odds were increased further with frequent cannabis use, or with concomitant tobacco smoking or e-cigarette use (103025). Similarly, a larger epidemiological study in adults 18-74 years of age suggests daily cannabis use is associated with a 42% increased odds of stroke when compared with non-use, with lower odds for less than daily use, regardless of prior history of cigarette or e-cigarette use (113092). However, cannabis was smoked by 74% of respondents; it is unclear if this association applies to other routes of administration. Population research has also found that hospitalization related to ischemic stroke is increased by 17% in recreational users of cannabis; this increase is independent of other potential causes (96378). However, not all research has found a link between cannabis use and stroke. A case-control study in stroke patients suggests that cannabis use is not associated with an increased risk of ischemic stroke or transient ischemic attack when adjusted for tobacco use (92666). Another retrospective study in adults undergoing urine toxicology screening did not find an association between cannabis use and incidence of acute ischemic stroke over a 2-year period (104379).
Meta-analyses of up to 3 observational studies in adults with recent total hip or knee arthroplasty suggest that a history of cannabis use is associated with a greater risk of postoperative cardiovascular complications, including thromboembolic events and cerebrovascular accidents, when compared with no history of cannabis use (115363).
Smoking cannabis can cause a dose-dependent 20% to 100% increase in heart rate that begins within 10 minutes of smoking and lasts for 2-3 hours (61840,92668,96378,96379). A retrospective study suggests that cannabis use, abuse, and dependence in teenagers is associated with cases of palpitations and arrhythmias such as ventricular fibrillation, atrial flutter, and atrial fibrillation (103026). Smoking cannabis might cause tachycardia by inhibiting vagal tone or by stimulating beta-adrenergic receptors (92667,92668,96378). Also, smoking cannabis appears to cause orthostatic hypotension or, conversely, modestly increase blood pressure in patients who are supine (92669,96378). Smoking cannabis has also been associated with 1 case of recurrent vasovagal syncope that required a dual chamber pacemaker implant and 6 cases of atrial fibrillation (96378,112925). Many of these acute effects of smoking cannabis decrease after continued use for several days to a few weeks (92670). However, abrupt cessation of cannabis might also increase blood pressure (96378).
Cannabis use has also been associated with bradycardia. In one case, an elderly male accidentally ate 3 cannabis cookies with a recommended serving of one eighth of a cookie. The bradycardia resulted in dizziness and faintness and was nearly fatal (111084). Cannabis use has also been associated with sinus arrest and heart block. In a review highlighting 11 case reports of severe bradyarrhythmia associated with cannabis consumption, 3 were due to third-degree heart block, 2 were due to second-degree heart block, and 6 were due to sinus arrest (108684). In an additional case report, a 2-year-old boy developed bradycardia with first-degree atrioventricular (AV) block which lasted 12 hours after accidentally consuming an unknown number of cannabis gummies containing THC (110237).
Regular use of cannabis has also been associated with cases of cannabis arteritis, a type of peripheral vascular disease, with some cases requiring amputation (61837,91910,108697,111088). There is some disagreement over whether cannabis use contributes to the development of arteritis. A review of over 50 cases of arteritis associated with cannabis use suggests that tobacco use was prevalent in most cases. Since the clinical and pathological features of arteritis are the same as those of thromboangiitis obliterans, which is associated with tobacco use, there is limited evidence to suggest that cannabis is a causative factor for arteritis (61872,96378). Still, symptoms worsened with use of cannabis in many cases, and disease progression was halted when cannabis was discontinued (96378). There is one case of cannabis arteritis in a middle-aged male who was not currently using tobacco; however, he smoked cannabis in blunt wraps, which contained nicotine. Symptoms resolved and did not recur following treatment with aspirin and nifedipine and avoidance of cannabis (111088). Cannabis discontinuation is recommended to prevent disease progression and avoid amputation (108697).
Cannabis use may be associated with myocarditis and myopericarditis. There have been at least 12 probable cases of myocarditis reported in the literature, usually based on temporal association and exclusion of other potential causes. In case reports, cannabis was used twice weekly for 3 months in one case and almost daily in others. Most individuals were males under 30 and recovered with treatment (110232,110236,111090,112926). There is at least one case of acute myocarditis with pericarditis in a 26-year-old male who smoked cigarettes and vaped cannabis daily (111090).
A case of ventricular bigeminy and a case of circulatory collapse have been considered to be related to treatment with a specific oromucosal spray containing THC and cannabidiol (CBD) (Sativex, GW Pharmaceuticals) (61759,61820).
There have also been several cases of rarer cardiovascular complications. A case of renal and spleen infarction following use of large amounts of cannabis and cocaine has been reported in a 24-year-old male with healthy arteries. The event may have been due to cannabis and cocaine-induced thrombosis (61889). A case of renal artery spontaneous dissection has also been reported (96378). Additionally, a case of spontaneous coronary artery dissection has been reported in a 61-year-old male with recent cannabis use and a history of hypertension (115366). There are at least 2 cases of diffuse alveolar hemorrhage associated with cannabis use, although, in both cases, contaminants and/or other drugs may have contributed (103018,111072). Anecdotal reports of central retinal vein occlusion, limb ischemia, and acute thrombosis of aorta have also been associated with cannabis use (96378,108694). The development of stress cardiomyopathy has been temporally related to the consumption of cannabis. In one patient, there was evidence of recurrence (96378). The development of non-ischemic dilated cardiomyopathy and cardioembolism has also been temporally related to the consumption of cannabis, as seen in a single case report describing a young male with no previous medical history (108689). There is also a single case report of pericardial effusion suspected to be related to vaping cannabis 1.5 mg daily, providing 95% THC, for 2 months. However, the presence of contaminants in the product could not be ruled out (110231).

Dermatologic ...Rarely, topical exposure to cannabis has resulted rarely in a rash and red, itchy skin (96389,115374). In addition, there are at least 4 reported cases of contact dermatitis and 6 cases of contact urticaria due to cannabis. One of these cases involved airborne allergic contact dermatitis confirmed with patch testing in a 25-year-old male within 30-60 minutes of smoking medical cannabis (112927). Type IV sensitization to cannabis during occupational exposure was also confirmed via patch testing in a 24-year-old female with previously confirmed allergies to rye, grasses, mugwort, and nickel (115374).
There is at least one case of Stevens-Johnson syndrome thought to be associated with use of cannabis in a 32-year-old female (111078). A case of erythema multiforme-like recurrent drug eruption, characterized by the presence of erythematous, scaly, vesiculobullous, and targetoid rash, has been reported in a 19-year-old male who smoked cannabis for about a year prior to developing the condition. Discontinuation of cannabis improved the condition, but symptoms recurred once cannabis use was re-initiated (91918).

Endocrine ...Small clinical studies suggest that smoking cannabis daily for 21 days increases caloric intake and causes weight gain in otherwise healthy adults who are heavy or casual cannabis smokers (92671). It is thought that cannabinoids in cannabis increase appetite by influencing the endogenous endocannabinoid system (61847). However, there is conflicting evidence regarding the effects of chronic cannabis smoking on caloric intake and body weight (61847,113019). Also, epidemiological research in the US has found that people with a history of cannabis use tend to have a lower body mass index when compared with never users (92672,101489).
Other epidemiological research suggests that cannabis use is associated with worsened glycemic control and an increased risk for serious complications in patients with diabetes. Observational research has found that people with type 1 diabetes that report recreational cannabis use have worsened glycemic control and a 2-fold increased risk for diabetic ketoacidosis (DKA) than those who do not report recreational cannabis use (99574,100305,100308). A case of recurrent DKA precipitated by cannabinoid hyperemesis syndrome has also been reported in a 21-year-old female with type 1 diabetes who used cannabis regularly (112928). A cohort study in adults with type 2 diabetes suggests that cannabis use is associated with a higher risk for diabetic nephropathy, myocardial infarction, and peripheral arterial occlusion when compared with no cannabis use (100307). It is not clear if these associations are due to cannabis use or to a difference in lifestyle and self-care behaviors (100305,100306). Risk-taking behaviors in general have been associated with worsened glycemic control and increased HbA1c (100308). More research is needed to clarify if a causal relationship exists between cannabis use and glycemic control.
Cannabis use has also been associated with at least 27 cases of acute pancreatitis (99582,108686). In one case report, a 30-year-old female developed acute pancreatitis at two different time periods after increasing the frequency of smoking cannabis (99582).

Gastrointestinal ...Smoking and ingesting cannabis can cause xerostomia, nausea, and vomiting (13,18,2619,61896,96384,96813,113016). Vaping cannabis has been reported to cause sore throat and bad taste in up to 35% of patients (101420). Cannabis has also been reported to cause oral candidiasis. There have been 2 case reports of tongue candidiasis attributed to dry mouth after heavy cannabis use (104487). A specific cannabis oromucosal spray (Sativex, GW Pharmaceuticals) can cause dry mouth, nausea, and bad taste (61759,61764,61820,61896,61909,108698). Less commonly, this cannabis product may cause red and white buccal mucosal patches to develop inside the mouth (61820). Clinical research in patients with chronic, cancer-related pain receiving prescription opioids has found that using this product for 2-5 weeks increases nausea by 43% and vomiting by 50% when compared with opioid treatment alone (108676).
Excessive and prolonged cannabis use (2-3 times daily over 2 years) can lead to cannabinoid hyperemesis syndrome (CHS). This condition is characterized by cyclic attacks of nausea and vomiting, often accompanied by abdominal pain. CHS does not seem to be alleviated by conventional antiemetic medicine (99585,101423,101424,111076,111080,111083,112929,115046,115372,115375). Some patients experiencing CHS report using extremely hot baths to temporarily reduce symptoms. In one case, the extreme water temperature caused repeated burns, resulting in sepsis and hospitalization (99585,101423,101424,111076,111080). Symptoms of CHS resolve only after a sustained period of abstaining from cannabis use (99585,101423,115046). CHS can also sometimes precipitate hypophosphatemia, which has been attributed to hyperventilation during CHS (99577,115375). CHS has been linked to severe complications such as electrolyte imbalances. There is at least one case of nephrolithiasis in a young adult with a history of daily cannabis use and nephrolithiasis. The nephrolithiasis was thought to be related to CHS-associated dehydration and electrolyte imbalance (111091). There are 3 case reports of young adults chronically using cannabis that died from complications of cannabis use and CHS (99585). CHS was also reported to precipitate diabetic ketoacidosis (DKA) in a 21-year-old female with type 1 diabetes who regularly used cannabis (112928).
Chronic cannabis use has also been associated with several cases of intussusception; however a causal mechanism and link has not been determined (103028). There are at least 22 reported cases of adult intussusception, with associated abdominal pain, vomiting, and diarrhea, possibly associated with the chronic use of cannabis. Most cases resolved spontaneously; however, some required laparoscopic/manual reductions (110233).
Although laboratory research has suggested that cannabis use can decrease gastrointestinal motility, observational research suggests that cannabis use is associated with 30% reduced odds of constipation and no change in the likelihood for diarrhea (101485).
In one case report, a 26-year-old male with a 6-month history of daily cannabis use required cholecystectomy for gangrenous acalculous cholecystitis, presenting as persistent abdominal pain and intractable vomiting (115381).

Genitourinary ...The chronic use of cannabis can cause abnormal menstruation (18). Cannabis use has been associated with priapism in a few case reports. There is also some speculation that cannabis use might precipitate a priapism attack in patients with sickle cell trait (99584). However, it is too early to know if a causal relationship exists.
Meta-analyses of 3 observational studies in adults with recent total hip or knee arthroplasty suggests that a history of cannabis use is associated with a greater risk of postoperative urinary tract infections when compared with no history of cannabis use (115363).

Hematologic ...A few cases of intracerebral hemorrhage have been associated with cannabis use. In some but not all cases, reversible vasoconstriction syndrome was associated with intracerebral hemorrhage (96800). Some population research suggests that cannabis use is associated with an 18% increased risk of developing an aneurysmal subarachnoid hemorrhage, independent of other risk factors. However, other population research does not support these findings (96378).
Meta-analyses of up to 4 observational studies in adults with recent total hip or knee arthroplasty suggests that a history of cannabis use is associated with a greater risk of postoperative thromboembolic events, as well as a greater need for postoperative transfusions, when compared with no history of cannabis use (115363). Additionally, a retrospective chart review in adults undergoing chest masculinization surgery suggests that a history of cannabis use is associated with 3.5-fold greater odds of postoperative hematoma when compared with no cannabis use (115378).

Hepatic ...There is at least one case of acute hepatitis likely related to the chronic use of cannabis (110234).
Intravenously, cannabis may cause toxic hepatitis (61705).

Immunologic ...Oral, topical, and occupational exposure to cannabis has been associated with reports of sensitization and allergic reactions. A specific allergen in cannabis has not been identified. Exposure to cannabis smoke can also cause nasal congestion, runny nose, sneezing, coughing, and wheezing, possibly related to an allergic response in some individuals (96389).
Cases of topical and airborne contact dermatitis have been reported after cannabis exposure (112927,115374). There has also been at least one case of Stevens-Johnson syndrome (111078) and a case of erythema multiforme-like eruption (91918) thought to be associated with cannabis use. Additionally, an asthma attack has been reported in a 51-year-old male who inhaled cannabis seeds (61813).

Musculoskeletal ...Meta-analyses of up to 3 observational studies in adults with recent total hip or knee arthroplasty suggests that a history of cannabis use is associated with a greater risk of postoperative surgical revision, dislocation, mechanical loosening of prosthesis, periprosthetic fracture, and infection when compared with no history of cannabis use (115363).
Chronic use of large amounts of cannabis has been associated with alterations in bone metabolism. In one case report, a 56-year-old male patient who had smoked up to 7 grams of cannabis daily for 25 years presented with osteoporosis and multiple vertebral crush fractures (92673).
A 26-year-old male developed hypokalemia-induced progressing paralysis, followed by rhabdomyolysis, thought to be related to recreational cannabis use (110238).
Orally, in children ages 12 years and younger, accidental ingestion of cannabis-containing edibles has been associated with ataxia, tremors, hypotonia, hypothermia, nystagmus, respiratory depression, and seizures (103793). Legalization of recreational cannabis has been associated with an increased rate of poisoning from cannabis edibles (104492).

Neurologic/CNS ...Smoking, vaping, or ingesting cannabis can cause headache, dizziness, numbness, disorientation, somnolence, and fatigue (17371,61896,96384,96813,101420,113016). Recurrent, strong headaches associated with cannabis use might be related to reversible cerebral vasoconstriction syndrome (RCVS). In one cohort, 32% of individuals with RCVS were cannabis users (96378). Meta-analyses of 2 observational studies in adults with recent total hip or knee arthroplasty suggests that a history of cannabis use is associated with a greater risk of postoperative cerebrovascular accidents when compared with no history of cannabis use (115363).
Intoxicating doses of cannabis impair reaction time, motor coordination, declarative memory, and visual perceptions, and can also produce panic reactions and other emotional disturbances. An individual's driving ability can be impaired for up to 8 hours (18,61896,103023). One small clinical trial shows that inhaling vaporized cannabis containing delta-9- tetrahydrocannabinol (THC) 10 mg, alone or with cannabidiol (CBD) 10-30 mg, modestly impairs verbal recall (110242). A small prospective study has found that inhaling vaporized cannabis containing THC 13.75 mg or THC/cannabidiol 13.75 mg increases lane weaving for the first 100 minutes when compared with placebo. This impairment was comparable to that of a blood alcohol concentration of 0.05%, which is considered to indicate clinically relevant impairment (104482). The validity of this finding is limited because the study only tested a single dose of cannabis, which does not mimic typical real-world use (104484). Acute use of cannabis has also been associated with increased motor collision risk (61911,61904), especially if the driver is using alcohol or other drugs concomitantly (103024). Two retrospective studies suggest that state-based legalization and commercialization of cannabis is associated with increased traffic fatalities. Based on this data, experts predict that nationwide cannabis legalization could result in 6,800 more traffic fatalities per year. The increase in traffic fatalities may vary state to state. For example, one study found an increase in fatalities in Colorado but not in Washington state (103022,103024,103027). These studies are limited due to their retrospective nature and a lack of control over other confounding factors such as out-of-state cannabis tourism that could have affected driving fatalities.
Inhalation of highly potent cannabis might sometimes cause intoxication similar to serotonin syndrome. In 2 case reports, patients presented to the emergency room with dilated pupils, lower extremity rigidity, and clonus after smoking a highly potent form of cannabis (103016). Another case reports a 20-year-old male taking cannabis and fluoxetine who presented with 2 episodes of serotonin syndrome that were not correlated to changes in fluoxetine administration (112923).
Two cases of paralysis secondary to hypokalemia are reported, likely due to coupling of cannabinoid receptors to potassium channels; both patients had complete resolution of symptoms after potassium replacement (110238,112930).
When smoked chronically and in large amounts, cannabis might cause seizures. Two cases report adult males smoking cannabis, one in the form of "moon rock," who presented with secondary generalized tonic-clonic seizures that were managed with medications (99580,113013). Additionally, there have been 2 cases of new-onset seizures in pediatric patients reported after accidental ingestion of cannabis-containing edibles (103794).
Cannabis-induced acute encephalopathy has been found in a 94-year-old female given cannabis by a family member. The cannabis had been marketed as being pure cannabidiol (CBD); however, a urinary analysis tested positive for delta-9-tetrahydrocannabinol (THC). Symptoms included confusion and disorientation, hallucinations, and diarrhea (111071). A case of acute hippocampal encephalopathy has been reported in a 24-year-old male with a history of heavy cannabis use (8 to 10 joints daily for 6 years) who presented to the emergency department with a nonfebrile status epilepticus and diminished consciousness, requiring intubation and admission to the intensive care unit (115379).
In one case report, early-onset frontotemporal dementia resulting in extreme behaviors (e.g., eating inedible objects, incontinence, mutism) was visualized with magnetic resonance imaging (MRI) in a 34-year-old male after 2 years of cannabis use; psychiatric and other neurodegenerative diagnoses were ruled out (113011).
Long-term use of cannabis can cause cognitive impairment, affecting executive function, learning and memory, and global cognition, that lasts longer than the period of acute intoxication (10242,61844,101488). These cognitive impairments develop slowly and worsen as the years of cannabis use increase, with some research suggesting they become clinically significant after about 2 decades of use (10242).
Using oromucosal spray containing cannabis extract (Sativex, GW Pharmaceuticals) can cause dizziness, lightheadedness, sleepiness, and fatigue (61759,61764,61820,61896,61909,96814). Two clinical studies in adults with cancer show that non-inhaled medical cannabis has a negative effect on mental concentration when compared with control (115355).
Limited research shows that consuming large amounts of CBD might increase the adverse effects of THC. A small study in healthy adults shows that consumption of brownies containing THC 20 mg plus cannabidiol (CBD) 640 mg increases feelings of sedation and memory impairment when compared to consuming brownies containing only THC 20 mg (111092).
Prospective, observational research in children who were 12 years old at the time of enrollment suggests that cannabis use is associated with poorer sleep quality at 18 years of age. Additionally, more recent use at age 18 years was associated with a greater reduction in sleep quality (101428). In children ages 12 years and younger, accidental ingestion of cannabis-containing edibles has been associated with lethargy, seizures, and coma (103793,103794). Legalization of recreational cannabis has been associated with an increased rate of poisoning from cannabis edibles (104492).
A meta-analysis of observational studies suggests that prenatal cannabis use is associated with a greater risk of attention deficit hyperactivity disorder (ADHD) or ADHD symptoms and autism spectrum disorder in the offspring when compared with no exposure (115356).

Ocular/Otic ...The use of inhaled cannabis can cause a characteristic reddening of the eyes (2619,96389). Smoking cannabis can also cause dry eyes (17371). Acute poisoning from cannabis can cause lacrimation (18). Orally, in children ages 12 years and younger, accidental ingestion of cannabis-containing edibles has been associated with nystagmus (103793,103794). A case of bilateral optic neuropathy was reported in a 28-year-old male, 8 hours after smoking cannabis and cigarettes. Treatment involved high-dose corticosteroids, aspirin, and complete abstinence from cannabis use (115368).
Observational research suggests that cannabis use at least once per month increases the risk for tinnitus. The severity of tinnitus does not appear to be correlated to the quantity or frequency of cannabis use (101486).

Oncologic ...There is some concern that cannabis use increases the risk for cancer. A meta-analysis of observational case-control studies suggests that cannabis is not associated with an increased risk for head and neck squamous cell carcinoma or oral cancer. However, more than 10 years of cannabis use is associated with an increased risk for testicular germ cell tumor (101430).
Any correlation between cannabis use and lung cancer risk is unclear. Evidence from a case-control study suggests that smoking cannabis increases the risk of lung cancer by 8% for each joint-year of smoking (61829). However, other observational research did not find an association between duration, intensity, or cumulative smoking of cannabis and lung cancer (99590). A meta-analysis of case-control studies could not clarify this association due to the poor methodological quality and reporting of the available research (101430). More data is needed to determine if there is a link between specific types of lung cancer and smoking cannabis.
Two observational studies in adults with cancer who were receiving immunotherapy suggest that using cannabis and/or cannabinoids may worsen outcomes. In one observational study, adults with advanced cancer who used cannabis had a shorter time to cancer progression and shorter average overall survival. In a retrospective review, adults with advanced cancer who used cannabis had similar progression and survival rates, but a reduced response to immunotherapy treatment (115047).

Psychiatric ...When used short-term, smoking cannabis or using oromucosal spray containing cannabis extract (Sativex, GW Pharmaceuticals) can cause anxiety or paranoid thinking or dissociation (61896,96814). One small clinical trial shows that inhaling vaporized cannabis containing delta-9- tetrahydrocannabinol (THC) 10 mg, alone or with cannabidiol (CBD) 10-30 mg, modestly induces psychotic symptoms (110242). However, a single dose of inhaled cannabis containing an increased ratio of CBD to THC seems to result in reduced feelings of anxiety when compared to a higher ratio of THC to cannabidiol (110254).
Vaporized cannabis also seems to reduce motivation. In a clinical study in healthy adults, inhaling vaporized cannabis containing 8 mg THC with or without CBD 10 mg and repeating half the dose 1.5 hours later, reduces motivation when compared to placebo (99583).
The chronic use of cannabis can cause apathy, psychic decline, psychosis, and sexual dysfunction (18,113013). Cannabinoids can increase anxiety, confusion, and hallucinations (96384).
Cannabis use can be habit-forming. Meta-analyses of the available research suggest that as many as 47% of regular cannabis users develop some form of dependence, and up to 9% of all users develop cannabis use disorder (101701,102801). Another meta-analysis of clinical and observational studies suggests that the prevalence of cannabis use disorder is 25% among individuals who use medicinal cannabis (115360). An additional meta-analysis of observational research suggests that the risk of cannabis use disorder is positively associated with frequency of use (110228). In patients with cannabis dependence, cessation of use can precipitate cannabis withdrawal within 1-2 days. The risk for cannabis withdrawal syndrome seems to be greater in males, those with higher cannabis use, and those with concomitant drug or tobacco use (102801). Symptoms of cannabis use withdrawal typically last for 7-14 days and include irritability, nervousness, difficulty sleeping, decreased appetite, and depressed mood. Physical symptoms such as stomach pain, tremors, sweating, fever, or headache might also occur. Severity of withdrawal varies, and largely depends on the cumulative amount of cannabis used prior to cessation (99576,101702). Withdrawal symptoms may be particularly problematic in individuals with pre-existing depression or anxiety, resulting in failed cessation attempts (102801). Psychosis has been reported rarely as a withdrawal symptom. In one case report, a 32-year-old female with a 22-year history of consistent and heavy cannabis use experienced 2 psychotic episodes, each following cessation of use for 1 week (110227). In other case reports, 3 young male adults with a history of chronic cannabis use experienced a manic episode with psychosis following abrupt discontinuation of cannabis use (115382).
Observational and population research suggests that using cannabis is associated with increased risk of developing psychotic symptoms or a psychotic condition, particularly in males and/or patients with preexisting psychosis propensity (61810,61812,61850,61873,61888,61891,96381,108687,111097). One case report also suggested a potential relationship between cannabis use and antepartum psychosis in a patient with pre-eclampsia (115377). This increased risk for psychosis might be attributed to the THC content in cannabis (103021,108687). Observational research suggests that cannabis use is associated with about a 2-fold increased risk of psychosis when compared to never using cannabis (96381). Case-control observational research suggests that cannabis use is associated with a 3-fold increased risk for a first-episode psychosis; daily use of high-potency cannabis was associated with a nearly five-fold increased risk for first-episode psychosis when compared with never using cannabis (101426). Similarly, a meta-analysis of observational research in adolescents suggests that cannabis use is associated with an increased risk of psychosis, with an even greater risk observed in adolescents with a history of childhood trauma, heavier and more frequent use, and those who began using at an earlier age (108687).
Cannabis may also increase the risk of relapse in patients with psychotic disorders, with longer hospital admissions and more severe symptoms compared with nonusers and discontinued users (61848,96382). Furthermore, using cannabis appears to be associated with a 3-fold increased risk of new onset mania (91912). Cannabis use, usually heavy, has also been associated with cases of catatonia in children and adults with or without a previous history of psychiatric illness (104493,104494,108683,111086,113012,115365). In two of these cases, management with electroconvulsive therapy and lorazepam was successful (113012,115365).
Use of cannabis is associated with depression, panic attacks, anxiety, obsessive-compulsive disorder (OCD), and suicide ideation/attempt. In one case, a 32-year-old male chronic cannabis user of about 10 years developed panic attacks. His symptoms had started about 2 years previously. He had recently abstained from cannabis use and had no past history of mental illness (111077). In one case, a 22-year-old male with no previous psychiatric history developed symptoms of OCD after 2-3 months of consistent cannabis use, with worsening of symptoms when cannabis use increased. Symptoms disappeared when the patient abstained from use and recurred when use resumed (115361). Use of cannabis, at least once weekly, has been associated with an increased risk of developing depression. In patients with depression, cannabis use is associated with worsened symptoms and increased suicidal ideation. However, due to the retrospective nature of these studies it is not clear whether depression resulted in increased cannabis use or if the cannabis use worsened or triggered depression. Having depression is associated with an increased odds of cannabis use, especially more frequent daily use, when compared with people without depression (91916,99575,104488,115362). Population research also suggests that using cannabis is associated with 24% increased odds of anxiety when compared to never using cannabis (96386). A meta-analysis of 6 prospective observational studies in adolescents with no pre-existing physical or mental health disorders suggests that cannabis use is associated with 2-fold greater odds of developing an anxiety disorder when compared with adolescents without cannabis exposure (115359). Additionally, clinical research in adults with cancer shows that higher doses of synthetic THC increase the likelihood of anxiety events by about 2-fold when compared with lower doses (115355).
Observational research in young adult chronic cannabis users suggests that smoking high potency cannabis, containing 10% or more of THC, is associated with greater risk of anxiety when compared with smoking lower potency cannabis (103795). The increased anxiety might also contribute to the 2-fold higher odds of youth violence seen with cannabis use when compared with non-use (104486). A meta-analysis of observational research in individuals aged 11-21 years suggests that cannabis smoking is associated with an approximate 2-fold increased risk of both suicidal ideation and attempt when compared with non-cannabis smoking (110229). Similarly, a meta-analysis of 15 observational studies in individuals aged 10-24 years suggests that recurrent cannabis use is associated with a 1.6 greater odds of suicidal ideation when compared with non-use (115357). Similarly, a large observational study of hospitalized adolescents suggests that cannabis use disorder is associated with a 40% increased odds of suicide attempt or self-harm (113015). Between 2009 and 2021, over 18,000 intentional, suspected suicidal cannabis exposures were reported to the National Poison Data System (NPDS) in children and adults aged 5 years and up. Death or another major outcome occurred in approximately 10% of all cases and in 19% of adults aged 65 years and up. Almost all cases occurred in individuals using at least one additional substance; therefore, a direct link cannot be made between cannabis use and attempted suicide (110324).
When consumed in large amounts, edible cannabis products containing at least 50 mg of THC have been associated with anxiety, abnormal behavior, psychosis, and suicidal tendencies (91914,103796). A case of erratic speech and hostile behaviors, followed by suicidal actions resulting in death, has been reported in a 19-year-old male who consumed an edible cannabis cookie. According to the product's label, the serving size should have been one-sixth of the cookie. This serving size would have contained 10 mg of THC. However, the decedent ate the entire cookie after not experiencing effects within 30-60 minutes of the initial dose (91914). Due to this case and other cases of overconsumption of edible cannabis products, in February 2015 the state of Colorado began requiring that edible cannabis products contain no more than 10 mg of THC per serving or that the products have clear demarcation of each 10-mg serving if they contain more than 10 mg of THC (91914). Additionally, a small study in healthy adults shows that oral consumption of brownies containing THC 20 mg plus cannabidiol (CBD) 640 mg increases feelings of anxiety, paranoia, and irritability, when compared to consuming brownies containing only THC 20 mg (111092).

Pulmonary/Respiratory ...Smoking or vaping cannabis can cause cough and bronchodilation (17371,61799,96378,96389,99581,101420). At least 5 cases of pneumomediastinum have been reported (61915,108679,110235,113014). These cases occurred in patients aged 19 to 27 years. In one case, cannabis was smoked the evening before symptoms occurred and in the others, cannabis was smoked daily or chronically; all cases made significant recoveries (61915,108679,110235,113014). There is also a case of hypersensitivity pneumonitis related to the use of cannabis; one day of corticosteroid treatment resulted in resolution (111089).
When smoked long-term, cannabis can cause laryngitis, bronchitis, phlegm, wheezing, and coughing (18,61799,61811,61855,96378,99581,110321). Using oromucosal spray containing cannabis extract may cause pharyngitis, hoarseness, and throat irritation (61759).
Acute eosinophilic pneumonia has been reported in at least four cases (110240,110241). A 21-year-old male reported using 20 homemade cannabis joints the evening before symptom onset which included respiratory distress and abdominal pain. An 88-year-old male developed cough and dyspnea after using 3 cannabis joints daily for 2 months to control pain (110240,110241). Acute respiratory distress syndrome was reported in a 25-year-old male with a history of smoking both cannabis and methamphetamine (115367). Chronic use of cannabis has also been associated with several cases of an unusual pattern of bullous emphysema (1395,61814,110235,115373). A healthy 17-year-old male with a history of illicit substance use was diagnosed with cannabis-induced thermal epiglottitis after presenting with acute airway obstruction (108682). In one case report, a 51-year-old male presented with drug-induced lung injury following daily cannabis smoking for over 20 years (111094). Heavy, chronic cannabis smoking has also been associated with a case of isolated pulmonary Langerhans cell histiocytosis in a 16-year-old male presenting with recurrent, spontaneous bilateral pneumothoraxes and cystic lesions on pulmonary imaging (108693). In another case, a small apical pneumothorax occurred in a 20-year-old male with a history of disordered cannabis use (110235). Similarly, spontaneous right-sided pneumothorax with bilateral apical blebs was reported in a 23-year-old male with a 5-year history of daily cannabis smoking (115048). Additionally, recurrent spontaneous pneumothorax, tension pneumothorax, and multiple apical blebs were reported in a 26-year-old male with a 10-12-year history of smoking cannabis 7 grams daily (115371).
Meta-analyses of 2 observational studies in adults with recent total hip or knee arthroplasty suggests that a history of cannabis use is associated with a greater risk of postoperative pneumonia and respiratory failure when compared with no history of cannabis use (115363).
Regular smoking of 3-4 cannabis cigarettes per day is reported to produce symptoms and airway histological effects similar to those seen with an average tobacco cigarette use of 20-22 per day (1395). A small clinical trial shows that inhaling a high-grade cannabis (Bedrocan International B.V., Veendam, The Netherlands) 100 mg, containing THC 21.8% and cannabinol 0.1%, does not produce respiratory depression (111096).
Any correlation between cannabis use and lung cancer risk is unclear. Evidence from a case-control study suggests that smoking cannabis increases the risk of lung cancer by 8% for each joint-year of smoking (61829). However, other observational research did not find an association between duration, intensity, or cumulative smoking of cannabis and lung cancer (99590). A meta-analysis of case-control studies could not clarify this association due to the poor methodological quality and reporting of the available research (101430). More data is needed to determine if there is a link between specific types of lung cancer and smoking cannabis.
Orally, in children ages 12 years and younger, accidental ingestion of cannabis-containing edibles has been associated with respiratory depression (103793,103794). In one case, a 5-week-old infant exposed to cannabis in utero and via breastmilk experienced recurrent apneic episodes. After switching to infant formula, the apnea improved (115370).

Renal ...Acute kidney injury has been reported after oral cannabis use. In one case, it was likely caused by pre-existing mild dehydration related to a lack of fluid intake, followed by cannabis-induced diarrhea (111071). Meta-analyses of 2 observational studies in adults with recent total hip or knee arthroplasty suggests that a history of cannabis use is associated with a greater risk of postoperative acute kidney injury when compared with no cannabis use (115363).
Acute eosinophilic pneumonia with acute renal failure has been reported in a 21-year-old male who reported using 20 homemade cannabis joints the evening before symptom onset (110240).
Cannabinoid hyperemesis syndrome (CHS) is characterized by cyclic attacks of nausea and vomiting, often accompanied by abdominal pain (99585,101423,101424). CHS has been linked to dehydration and electrolyte imbalances. There is at least one case of nephrolithiasis in a young adult with a history of daily cannabis use and nephrolithiasis. The nephrolithiasis was thought to be related to CHS-associated dehydration and electrolyte imbalance (111091).

Other ...Prenatal cannabis use has been associated with an increased risk of congenital birth defects in various organ systems. Cardiovascular birth defects include valve stenosis, septal defects, and Ebstein's anomaly; defects of the central nervous system include anencephaly, encephalocele, hydrocephaly, and microcephaly; genitourinary defects included renal agenesis and obstructive genitourinary defects (115358).

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