| Ingredients | Amount Per Serving |
|---|---|
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(Cannabis sativa Herb Extract, Cannabis sativa Whole Plant Extract)
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33.333 mg |
Water, Distilled, Starch, Modified, Coconut Oil, Fractionated, Lecithin, Natural & Artificial Flavors, Citric Acid
Below is general information about the effectiveness of the known ingredients contained in the product Hemp Derived CBD Tincture Spray 1000 mg Creamsicle Flavor. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Hemp Derived CBD Tincture Spray 1000 mg Creamsicle Flavor. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
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). 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, 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). 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 increased risk for psychological issues during adolescence (103792,104485). 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.
LIKELY SAFE ...when hemp seed, hemp protein, and hemp seed oil are used orally in food amounts. Hulled hemp seed, hemp seed protein powder, and hemp seed oil are generally recognized as safe (GRAS) in the US (100531).
POSSIBLY SAFE ...when hemp seed oil is used orally and appropriately as medicine, short-term. Hemp seed oil in doses of 2-6.3 grams daily has been safely used for 3-6 months (88183,16791,101145). Hemp seed oil in doses of 30 mL (27.6 grams) daily has been used safely for 2 months (101125). There is insufficient reliable evidence available about the safety of hemp oil, flowers, or leaves.
CHILDREN:
There is insufficient reliable information available about the safety of hemp in children.
Adverse effects have been noted in case reports, but details related to specific hemp products are limited (101153,110287).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Hemp Derived CBD Tincture Spray 1000 mg Creamsicle Flavor. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
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).
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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.
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Theoretically, cannabis might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs.
Details
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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).
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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).
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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).
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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).
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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).
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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).
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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).
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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).
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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).
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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).
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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).
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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).
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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).
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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).
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Theoretically, consuming hemp seed protein isolate with ACE inhibitors might have additive effects and increase the risk of hypotension.
Details
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Theoretically, hemp seed might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs.
Details
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Theoretically, hemp seed protein may have additive effects with antihypertensive drugs.
Details
In a hypertensive animal model, hemp seed protein hydrolysate reduced systolic blood pressure by a mechanism possibly involving the inhibition of renin and angiotensin converting enzyme (ACE) activities. However, there was no effect of hemp seed protein on blood pressure in normotensive animals (101136). Furthermore, hempseed oil consumption does not seem to reduce blood pressure in humans (101144).
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Theoretically, hemp might decrease the levels and clinical effects of CYP1A2 substrates.
Details
In vitro research shows that hemp induces CYP1A2 enzymes (111404).
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Theoretically, hemp might decrease the levels and clinical effects of CYP3A4 substrates.
Details
In vitro research shows that hemp induces CYP3A4 enzymes (111404).
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Theoretically, hemp might interfere with hormone therapy due to its estrogenic effects.
Details
In an ovariectomized animal model, a diet containing hemp seed 1%, 2%, or 10% resulted in normalized plasma levels of 17-beta-estradiol (101132). The mechanism of action for this effect is unclear.
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Below is general information about the adverse effects of the known ingredients contained in the product Hemp Derived CBD Tincture Spray 1000 mg Creamsicle Flavor. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
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 of age suggests daily cannabis use is associated with a 25% increased odds of MI when compared with nonuse, 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 forms of use. A case-control study suggests that there is a 4.8-fold increased risk of myocardial infarction within the first hour after smoking cannabis (91909). Also, there are cases of myocardial infarction that have occurred soon after smoking cannabis, although myocardial infarction 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 these events were associated with use of cannabis, or other cardiovascular risk factors such as cigarette smoking and/or being overweight (108692). However, there is at least one case where the individual experiencing a myocardial infarction following cannabis use did not have any other notable cardiovascular risk factors. This 16-year-old healthy male presented with chest pain and an acute myocardial infarction after smoking cannabis and drinking alcohol (99588). In another case, a 31-year-old male regular user of cannabis presented with a myocardial infarction. He had no prior known risk factor for cardiovascular disease; however, it was determined that he had an underlying myocardial bridge which may have increased his risk (111073). Another case reports a myocardial infarction with suspected spontaneous coronary artery dissection that resulted in cardiac arrest, cardiac catheterization, and discharge on medication in a previously healthy 36-year-old male with history of long-term marijuana use (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 or obesity and/or using tobacco (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 patients 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 that 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, an even 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 nonuse, 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 forms of use. 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).
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 delta-9-tetrahydrocannabinol (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 use of tobacco, there is limited evidence to support cannabis as being 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 did not currently use tobacco; however, he smoked marijuana in blunt wraps, a source of 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. However, death occurred in an infant (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 (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). There are at least 2 cases of diffuse alveolar hemorrhage associated with cannabis use (103018,111072). In a pediatric patient, it was unclear if the cause was cannabis smoke, cannabis contaminants, or the anesthetic agent sevoflurane (103018). In a 31-year-old male, it was thought to be related to the adulteration of cannabis with fentanyl (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. Treatment included aspirin 325 mg every 8 hours, colchicine 0.5 mg every 12 hours, and pantoprazole 40 mg every 12 hours (110231).
Dermatologic ...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). Topical exposure has resulted rarely in rash, and red and itchy skin (96389). 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 reports airborne allergic contact dermatitis confirmed with patch testing in a 25-year-old male within 30-60 minutes of smoking medical cannabis (112927). Also, 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).
Endocrine
...Evidence from preliminary clinical research suggests that smoking cannabis daily for 21 days increases caloric intake and causes weight gain in otherwise healthy patients 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 patients with type 1 diabetes that report recreational cannabis use have worsened glycemic control and a 2-fold increased risk for diabetic ketoacidosis than those who do not report recreational cannabis use (99574,100305,100308). 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). Also, a case of recurrent diabetic ketoacidosis precipitated by cannabinoid hyperemesis syndrome is reported in a 21-year-old female with type 1 diabetes who used cannabis regularly (112928).
Gastrointestinal
...Smoking and ingesting cannabis can cause xerostomia, nausea, and vomiting (13,18,2619,61896,96384,96813,113016).
It 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). Vaping cannabis has been reported to cause sore throat and bad taste in up to 35% of patients (101420).
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). 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). CHS can also sometimes precipitate hypophosphatemia, which has been attributed to hyperventilation during CHS (99577). 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 marijuana 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). Cannabinoid hyperemesis syndrome may be misdiagnosed as diabetic ketoacidosis (DKA), as seen in the case of a 21-year-old female with type 1 diabetes who regularly used cannabis and presented with recurrent DKA, abdominal pain, and cyclic vomiting which was ultimately CHS that precipitated ketosis (112928). Chronic cannabis use has also been associated with several cases of gastrointestinal intussusception; however a causal mechanism and link has not been determined (103028).
Orally, cannabis oromucosal spray (Sativex, GW Pharmaceuticals) can cause dizziness, 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).
There are at least 22 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).
Intravenously, cannabis can cause fulminant gastroenteritis (61705).
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.
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).
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, intravenous, 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). Also, 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).
Musculoskeletal
...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). Delta-9-tetrahydrocannabinol (THC) negatively impacts the survival of mesenchymal stem cells. These cells are present in bone marrow and involved in musculoskeletal repair processes (91911).
A 26-year-old man 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).
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 woman 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 reports early-onset frontotemporal dementia that resulted in extreme behaviors (e.g., eating inedible objects, incontinence, mutism) and was visualized with magnetic resonance imaging (MRI) in a 34-year-old male after 2 years of marijuana 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, becoming 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).
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).
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). 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). 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). Legalization of recreational cannabis has been associated with an increased rate of poisoning from cannabis edibles (104492).
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).
Evidence on whether cannabis use is linked with lung cancer risk is conflicting. 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.
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 cannabidiol to delta-9-tetrahydrocannbinol (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 delta-9-tetrahydrocannabinol (THC) with or without cannabidiol (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). An additional meta-analysis of observational research suggests that the risk of cannabis use disorder is 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 woman reporting at least a 22-year consistent and heavy use of cannabis experienced 2 psychotic episodes, each following cessation of use for 1 week (110227).
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). 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). In one of these cases, management with electroconvulsive therapy was successful (113012).
Use of cannabis is associated with depression, panic attacks, anxiety, 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). 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). Population research also suggests that using cannabis is associated with 24% increased odds of anxiety when compared to never using cannabis (96386). Incidence of anxiety seems to depend on the potency of the cannabis used.
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 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 other major outcome occurred in approximately 10% of all cases and 19.4% 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). 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). Chronic use of cannabis has also been associated with several cases of an unusual pattern of bullous emphysema (1395,61814,110235). 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).
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).
Evidence on whether smoking cannabis long-term may cause airway obstruction or lung cancer is conflicting (61799,61811). 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.
Using oromucosal spray containing cannabis extract may cause pharyngitis, hoarseness, and throat irritation (61759). An asthma attack has been reported in a 51-year-old male who inhaled cannabis seeds (61813).
Orally, in children ages 12 years and younger, accidental ingestion of cannabis-containing edibles has been associated with respiratory depression (103793,103794). However, a small clinical trial 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%, does not result in respiratory depression in healthy adults. Furthermore, it does not worsen oxycodone-induced respiratory depression (111096).
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).
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 marijuana use and nephrolithiasis. The nephrolithiasis was thought to be related to CHS-associated dehydration and electrolyte imbalance (111091).
Intravenously, cannabis may cause acute kidney failure (61705).
General
...Orally, hemp products are generally well tolerated in food amounts.
In larger amounts, hemp seed oil seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Rare cases of anaphylaxis have been reported. Long QT syndrome, torsades de pointes, and syncope have also been reported rarely.
Cardiovascular ...Acquired long QT syndrome, torsades de pointes, and syncope have been reported in a 56-year-old woman following the intake of supplements containing hemp oil. The hemp supplements provided cannabidiol (CBD), and possibly cannabigerol (CBG). Although the exact dose is unknown, up to six times the recommended dose had been used for approximately 6 weeks, in combination with a supplement containing berberine. While hospitalized, intravenous magnesium and saline were used to stabilize heart rhythm. It is unknown whether this adverse effect was related to the hemp oil, berberine, or their interaction (110104).
Hepatic ...Orally, there is a case report of elevated liver enzymes and hepatitis in a two-year-old boy given hemp extract 2. 5 mL, providing 125 mg phytocannabinoid, five to eight times daily for infantile spasms and refractory seizures. The total dose of phytocannabinoids was approximately 60-100 mg/kg daily (110287).
Immunologic
...Orally, there are case reports of allergy to hemp seed, although this is uncommon (101140,101154).
A 44-year-old male developed hives during a meal of hemp seed-crusted seafoods. Later, he developed facial swelling, shortness of breath, and problems speaking. Evaluation revealed allergy to a specific protein in hemp seed. He did not react to smoked cannabis (101140). In other cases, anaphylaxis, facial swelling, and worsening asthma have been reported in association with a first exposure to hemp seed, although some had smoked cannabis previously (101154).
Topically, a case of patch-test confirmed allergic contact dermatitis to hemp seed oil has been reported in a 22-year-old woman. The initial rash started at the application point on her back and spread to her arms, hands, and neck (110288).
Airborne exposure to hemp pollen is a relatively common cause of allergic respiratory symptoms in some locations (101155).
Neurologic/CNS ...Orally, cases of acute cannabinoid toxicity with neurological symptoms in children and adults have been associated with intake of hemp seed oil. There is a case report of decreased alertness, stupor, bloodshot eyes, and fixed gaze in a 2-year-old male probably related to the intake of one teaspoon hemp seed oil (CANAH) containing 0.06% delta-9-tetrahydrocannabinol (THC) twice daily for 3 weeks. After stopping the oil, irritability was reported over the next few days (101153).
