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Tx Effectiveness | Pt seeks evidence for specific condition
CA (N/V chemo, CA-assoc anorexia/cachexia, as CA tx, etc.) Evidence for CA and related conditions: - Chemo-induced N/V antiemesis
◦ Evidence for effectiveness of oral cannabinoids is conclusive or substantial [C][S].1
◦ Meta-analyses of controlled clinical trials support a beneficial effect of cannabinoids (nabilone [no longer available in the U.S.], dronabinol) on chemo-induced N/V.2
◦ NCCN3 includes cannabinoids as options for breakthrough chemo-induced N/V. There’s uniform NCCN consensus that the following interventions are appropriate, based on lower-level evidence [2A]; order doesn’t imply preference: dronabinol 5-10 mg PO tid-qid; Syndros (dronabinol sol) 2.1-4.2 mg/m^2/dose PO tid-qid; nabilone 1-2 mg PO bid (no longer available in the U.S.).
◦ Evidence is insufficient for cannabis for N/V prevention, and for cannabis in place of FDA-approved cannabinoids for N/V tx, in pts receiving chemo or radiation tx.4 - CA-assoc anorexia/cachexia syndrome. Insufficient/no evidence [I/N] for effectiveness of cannabinoids.1 No published studies on inhaled cannabis for appetite in CA pts.2
- CA-related pain. Insufficient evidence for effectiveness of cannabis.5
- CA tx. Insufficient/no evidence [I/N] for effectiveness of cannabinoids for tx of CAs, including glioma.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 NCI 2024. Cannabis and Cannabinoids (PDQ®)–Health Professional Version. National Cancer Institute. Updated July 17, 2024. Accessed July 23, 2024
3 NCCN 2024. Antiemesis (Version 1.2024). National Comprehensive Cancer Network. December 13, 2023. Accessed July 23, 2024
4 ASCO 2020. Hesketh PJ, et al. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020 Aug 20;38(24):2782-2797. Full-text PDF
5 VA 2017. Nugent SM, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. Primary Funding Source: U.S. Department of Veterans Affairs. Full-text article
Evidence for tx of pain and pain-related conditions:
- Chronic pain in adults
◦ Evidence for effectiveness of cannabis is conclusive or substantial [C][S]; effects are modest, per NAS.1 However, the majority of chronic pain studies in one review (Whiting et al., 2015) evaluated nabiximols outside the U.S.; little is known on the efficacy, dose, administration routes, or side effects of commonly used and commercially available cannabis products in the U.S.
◦ A VA-commissioned review2 found low-strength evidence that cannabis preparations w/ a precise THC component (most in a 1:1 or 2:1 ratio) may alleviate neuropathic pain, but evidence for other types of chronic pain is insufficient.
◦ A living, systematic review from AHRQ3 found low- to moderate-strength evidence of small improvements in pain (mostly neuropathic) and moderate to large increases in common adverse events (dizziness, sedation, nausea) w/ high- and comparable-THC:CBD-ratio extracted cannabinoids and synthetic products in the short term (1-6mo). Evidence for low-THC:CBD products, whole-plant cannabis, and other comparisons, outcomes, and plant-based compounds was unavailable or insufficient to draw conclusions. - CA-related pain. Insufficient evidence that cannabis is effective.2
- Central pain or painful spasms in MS. Oral cannabis extract is effective for ↓ central pain, and THC or nabiximols is probably effective for MS-related pain or painful spasms, but smoked marijuana is of unclear efficacy for ↓ pain.4
- Fibromyalgia. No convincing, unbiased, high-quality evidence was found that nabilone (no longer available in the U.S.) is valuable, and tolerability in fibromyalgia pts was low, per a Cochrane review;5 no relevant studies of herbal cannabis were identified. A VA-commissioned review2 found insufficient evidence for cannabis effectiveness for fibromyalgia and other mixed pain conditions, which include rheumatoid arthritis and inflammatory abd pain.
- Sleep disturbance due to fibromyalgia or chronic pain. Moderate evidence [M] that cannabinoids (primarily nabiximols) improve short-term sleep outcomes.1
- Depression in chronic pain pts. Limited evidence [L] that nabilone (no longer available in the U.S.), nabiximols, and dronabinol are ineffective for ↓ depressive sx in chronic pain pts.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 VA 2017. Nugent SM, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. Primary Funding Source: U.S. Department of Veterans Affairs. Full-text article
3 AHRQ 2024. Chou R, et al. Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain: 2023 Update—Surveillance Report 3. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 75Q80120D00006.) AHRQ Publication No. 24-EHC018. Rockville, MD: Agency for Healthcare Research and Quality; April 2024. Accessed July 23, 2024
4 AAN 2014. Koppel BS, et al. Systematic Review: Efficacy and Safety of Medical Marijuana in Selected Neurologic Disorders: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Apr 29;82(17):1556-1563. Free, full-text PDF at PubMed® Central
5 Walitt B, et al. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016 Jul 18:7(7):CD011694. Free, full-text PDF at PubMed® Central
Neuro conditions (MS, epilepsy, spasticity, etc.) MS-related conditions: spasticity, depression, etc. Evidence for MS: - MS spasticity
◦ Evidence for effectiveness of oral cannabinoids is conclusive or substantial [C][S] for improving pt-reported spasticity sx and is limited [L] for clinician-measured spasticity, per NAS.1
◦ AAN concluded oral cannabis extract ↓ pt-reported scores, and is probably ineffective for ↓ objective measures at 12-15wk but possibly effective at 1y. THC is probably effective for ↓ pt-reported scores, and is probably ineffective for ↓ objective measures at 15wk but possibly effective at 1y. Nabiximols is probably effective for ↓ pt-reported scores and probably ineffective for ↓ objective measures at 6wk. AAN concluded that smoked marijuana was of uncertain efficacy (insufficient evidence).2 - Central pain or painful spasms in MS. Oral cannabis extract is effective for ↓ central pain, and THC or nabiximols is probably effective for MS-related pain or painful spasms, but smoked marijuana is of unclear efficacy for ↓ pain.2
- Tremor in MS. THC and oral cannabis extract are probably ineffective; nabiximols is possibly ineffective.2
- Bladder dysfxn in MS. Nabiximols is probably effective for ↓ # of bladder voids/day at 10wk but is of unknown efficacy for ↓ overall bladder sx (conflicting studies); THC and oral cannabis extract are probably ineffective for bladder complaints.2
- Sleep disturbance in MS. Moderate evidence [M] that cannabinoids (primarily nabiximols) improve short-term sleep outcomes.1
- Depression in MS. Limited evidence [L] that nabilone (no longer available in the U.S.), nabiximols, and dronabinol are ineffective for ↓ depressive sx in MS.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 AAN 2014. Koppel BS, et al. Systematic Review: Efficacy and Safety of Medical Marijuana in Selected Neurologic Disorders: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Apr 29;82(17):1556-1563. Free, full-text PDF at PubMed® Central
Non-MS conditions: epilepsy, spasticity, dystonia, Tourette, ALS, TBI, intracranial hemorrhage, Huntington, Parkinson, dementia Evidence for various conditions: - Epilepsy. Insufficient/no evidence [I/N] for effectiveness of cannabinoids;1 data on cannabinoids to ↓ sz frequency are insufficient.2
- Dementia. Limited evidence [L] that cannabinoids are ineffective for improving dementia-assoc sx.1
- Tourette. Limited evidence [L] on THC capsules improving sx;1 data on THC for ↓ tic severity are insufficient.2
- Dystonia. Insufficient/no evidence [I/N] that nabilone (no longer available in the U.S.) and dronabinol are effective;1 data on dronabinol for cervical dystonia are insufficient.2
- Spasticity in spinal cord-injury paralysis. Insufficient/no evidence [I/N] that cannabinoids are effective.1
- Parkinson. There’s insufficient/no evidence [I/N] that cannabinoids are effective for Parkinson motor sx or levodopa-induced dyskinesia, per NAS.1 AAN2 concludes that oral cannabis extract is probably ineffective for levodopa-induced dyskinesias.
- Huntington. There’s insufficient/no evidence [I/N] that oral cannabinoids are effective for chorea and certain neuropsych sx, per NAS.1 AAN2 concludes that studies were underpowered, so no reliable conclusions can be drawn.
- ALS sx. Insufficient/no evidence [I/N] that cannabinoids are effective.1
- TBI/Intracranial hemorrhage. Limited evidence [L] exists for cannabinoids and a statistical association w/ better outcomes (i.e., mortality, disability).1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 AAN 2014. Koppel BS, et al. Systematic Review: Efficacy and Safety of Medical Marijuana in Selected Neurologic Disorders: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Apr 29;82(17):1556-1563. Free, full-text PDF at PubMed® Central
Behavioral/Mental Health conditions (anxiety, addiction, PTSD, sleep, etc.) Evidence for addiction tx: - Achieving abstinence. There’s insufficient/no evidence [I/N] that cannabinoids are effective in achieving abstinence from addictive substances.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
Evidence for anxiety or depression: - Anxiety. Evidence is limited [L] that CBD is effective for improving anxiety sx, as assessed by a public speaking test, in individuals w/ social anxiety disorders.1
- PTSD. There’s limited evidence [L] (from a single, small, fair-quality trial) that nabilone (no longer available in the U.S.) is effective, per NAS.1 A VA-commissioned review2 found insufficient evidence (lack of efficacy trials) on cannabis for PTSD, and notes that info on harms is limited.
- Depression in chronic pain or MS pts. Limited evidence [L] shows that nabilone (no longer available in the U.S.), nabiximols, and dronabinol are ineffective for ↓ depressive sx in pts w/ chronic pain or MS.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 VA 2017. O’Neil ME, et al. Benefits and Harms of Plant-Based Cannabis for Posttraumatic Stress Disorder: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):332-340. Full-text article
Evidence for schizophrenia: - Schizophrenia or schizophreniform psychosis. There’s insufficient/no evidence [I/N] that CBD is effective for mental health outcomes.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
Evidence for eating disorders: - Anorexia nervosa. There’s insufficient/no evidence [I/N] that cannabinoids are effective.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
Evidence for sleep disorders: - Sleep disturbance due to OSA, fibromyalgia, chronic pain, or MS. There’s moderate evidence [M] that cannabinoids (primarily nabiximols) improve short-term sleep outcomes.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
GI conditions (N/V, irritable bowel, anorexia/wt loss, etc.) Evidence for GI conditions: - Chemo-induced N/V antiemesis
◦ Evidence for effectiveness of oral cannabinoids is conclusive or substantial [C][S].1
◦ Meta-analyses of controlled clinical trials support a beneficial effect of cannabinoids (nabilone [no longer available in the U.S.], dronabinol) on chemo-induced N/V.2
◦ NCCN3 includes cannabinoids as options for breakthrough chemo-induced N/V. There’s uniform NCCN consensus that the following interventions are appropriate, based on lower-level evidence [2A]; order doesn’t imply preference: dronabinol 5-10 mg PO tid-qid; Syndros (dronabinol sol) 2.1-4.2 mg/m^2/dose PO tid-qid; nabilone 1-2 mg PO bid (no longer available in the U.S.).
◦ Evidence is insufficient for cannabis for N/V prevention, and for cannabis in place of FDA-approved cannabinoids for N/V tx, in pts receiving chemo or radiation tx.4 - Nausea of pregnancy. Marijuana use not recommended during pregnancy; linked to lower birth wt and ↑risk of preterm birth; may also affect fetal brain development.5
- CA-assoc anorexia/cachexia syndrome. Insufficient/no evidence [I/N] for effectiveness of cannabinoids.1 No published studies on inhaled cannabis for appetite in CA pts.2
- HIV/AIDS-assoc low appetite and wt loss: Limited evidence [L] that cannabis and oral cannabinoids are effective for ↑ appetite and ↓ wt loss.1
- Anorexia nervosa. Insufficient/no evidence [I/N] that cannabinoids are effective.1
- IBS sx. Insufficient/no evidence [I/N] that dronabinol is effective.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 NCI 2024. Cannabis and Cannabinoids (PDQ®)–Health Professional Version. National Cancer Institute. Updated July 17, 2024. Accessed July 23, 2024
3 NCCN 2024. Antiemesis (Version 1.2024). National Comprehensive Cancer Network. December 13, 2023. Accessed July 23, 2024
4 ASCO 2020. Hesketh PJ, et al. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020 Aug 20;38(24):2782-2797. Full-text PDF
5 NIDA 2019. Cannabis (Marijuana) DrugFacts. National Institute on Drug Abuse. Updated December 2019. Accessed July 23, 2024
Ocular conditions: glaucoma Evidence for glaucoma: - Intraocular pressure
◦ There’s limited evidence [L] that cannabinoids are ineffective for improving IOP in glaucoma, per NAS.1
◦ AGS2 notes that marijuana can temporarily lower IOP, but side effects, short duration of action, and lack of evidence for altering glaucoma course preclude recommending marijuana, in any form, for glaucoma tx.
◦ AAO3 found no scientific evidence of ↑benefit and/or ↓risk of marijuana for glaucoma tx, vs. available pharmaceutical agents.
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 AGS 2009. Jampel H. Position Statement on Marijuana and the Treatment of Glaucoma. American Glaucoma Society. August 10, 2009. Accessed July 24, 2024
3 AAO 2014. Schwab IR, et al; American Academy of Ophthalmology Complementary Therapy Task Force. Complementary Therapy Assessment: Marijuana in the Treatment of Glaucoma. American Academy of Ophthalmology. June 2014. PDF
AAO 2023. Turbert D, Gudgel D. Does Marijuana Help Treat Glaucoma or Other Eye Conditions? American Academy of Ophthalmology. December 13, 2023. Accessed July 24, 2024
AAO 2023. Kern D. Infographics: Why Eye Doctors Don’t Recommend Marijuana for Glaucoma. American Academy of Ophthalmology. December 13, 2023. Accessed July 24, 2024
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Risks of Use | Pt seeks evidence on specific health risk
Drug ⇔ cannabis/cannabinoid interaction risks Evidence for drug interaction risks: - Drugs metabolized by P450 system. Cannabinoids interact w/ hepatic cytochrome P450 enzymes;1,2 substances that inhibit or induce P450 enzymes may alter drug adverse effects or efficacy.
THC, CBD, and cannabinol inhibition/induction studies on major human CYP-450 isoforms generally reflect a low risk for clinically significant drug interactions w/ most use; however, specific human data are lacking. Given variability of cannabis products, routes, doses, and other factors, interactions are expected to vary.2
In vitro data characterizing CYP-450 enzymes as potential significant contributors to primary metabolism:2
◦ THC: 2C9, 3A4
◦ CBD: 2C19, 3A4
◦ Cannabinol: 2C9, 3A4
Clinical data on CYP-450 enzymes:2
◦ 2C9. Pharmacogenetic data support 2C9 as a significant contributor to THC metabolism.
◦ 3A4. A pharmacokinetic interaction study between ketoconazole ⇔ oromucosal cannabis extract supports 3A4 as a significant metabolic pathway for THC and CBD.
◦ 2C19. Absence of interaction between CBD in oromucosal cannabis extract ⇔ omeprazole suggests a less significant role for 2C19 in CBD metabolism.
◦ 1A2. Smoked marijuana appears to induce theophylline clearance, but the specific role of cannabinoids in this effect is questionable. - CNS depressants. Additive effects may occur when cannabinoids are taken w/ alcohol or other CNS depressants.
- ADHD stimulants. There’s substantial evidence [S] that ADHD stimulant tx during adolescence is not a risk factor for problem cannabis-use development.3
- CA tx. In 1 study of CA pts treated w/ IV irinotecan or docetaxel, concomitant administration of cannabis herbal tea didn’t influence irinotecan or docetaxel exposure or clearance.1
Footnotes 1 NCI 2024. Cannabis and Cannabinoids (PDQ®)–Health Professional Version. National Cancer Institute. Updated July 17, 2024. Accessed July 23, 2024
2 Stout SM, Cimino NM. Exogenous Cannabinoids as Substrates, Inhibitors, and Inducers of Human Drug Metabolizing Enzymes: A Systematic Review. Drug Metab Rev. 2014 Feb;46(1):86-95. PubMed® abstract
3 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
Problem cannabis-use risks Problem cannabis use encompasses various levels of hazardous/potentially harmful use patterns (e.g., cannabis use d/o, dependence, abuse). Cannabis use d/o, a diagnosable psychiatric condition, is a problematic cannabis use pattern that leads to clinically significant personal, social, physical, and/or psychological distress or impairment.1 Evidence for the risk of problem cannabis use: - Frequency of cannabis use. There’s substantial evidence [S] for a statistical association between ↑frequency of cannabis use and the development of problem cannabis use.1
- Age of cannabis initiation. Substantial evidence [S] supports a statistical association between earlier age at cannabis-use initiation as a risk factor for developing problem cannabis use.1 People who begin using marijuana before they’re 18 yo are 4-7x more likely to develop marijuana use d/o than adults.2
- Adolescent factors. There’s moderate evidence [M] of the following risk factors for developing problem cannabis use: adolescent cannabis-use frequency, oppositional behaviors, younger first-alcohol use, nicotine use, parental substance abuse, poor school performance, antisocial behaviors, and childhood sexual abuse.1
- Nicotine and alcohol. Substantial evidence [S] supports cigarette smoking as a risk factor for progressing to problem cannabis use. Moderate evidence [M] shows that neither alcohol nor nicotine dependence alone is a risk factor for progression from cannabis use to problem cannabis use.1
- Combo drug abuse. There’s moderate evidence [M] for combined use of abused drugs as a risk factor for developing problem cannabis use.1
- Male/female. Being male is a risk factor for developing problem cannabis use [M]; for progressing from cannabis use to problem cannabis use [S]; and for ↑severity of problem cannabis use, although recurrence of problem cannabis use doesn’t differ between males and females [S].1
- ADHD. There’s moderate evidence [M] that adolescent ADHD isn’t a risk factor for problem cannabis use; substantial evidence [S] exists for ADHD stimulant tx during adolescence not being a risk factor for problem cannabis-use development.1
- Anxiety, mood, and personality disorders1
◦ Childhood anxiety/depression. Limited evidence [L] for them being risk factors for problem cannabis use.
◦ Major depressive d/o. Moderate evidence [M] for it being a risk factor for developing problem cannabis use.
◦ Anxiety, personality disorders, bipolar disorders. Moderate evidence [M] that they aren’t risk factors for developing problem cannabis use.
◦ PTSD. Moderate evidence for a statistical association between ↑PTSD sx severity and problem cannabis use. - Hx psychiatric tx. Moderate evidence [M] supports a statistical association between hx of psychiatric tx and persistent problem cannabis use.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 NIDA 2019. Cannabis (Marijuana) DrugFacts. National Institute on Drug Abuse. Updated December 2019. Accessed July 23, 2024
Problem-use risks of substances other than cannabis Evidence for the risk of problem use of other substances: - Substance dependence/substance use d/o
◦ Moderate evidence [M] supports a statistical association between cannabis use and development of substance dependence/substance use d/o (including alcohol, tobacco, illicit drugs), per NAS.1 Similarly, a VA-commissioned review2 concluded that cannabis use is assoc w/ risk for incident alcohol and other substance use disorders.
◦ Limited evidence [L] exists for a statistical association between cannabis use and tobacco-use initiation.1 - Changes in rates/patterns of other substance use. There’s limited evidence [L] for a statistical association between cannabis use and changes in rates/patterns of other licit/illicit substance use.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 VA 2017. Nugent SM, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. Primary Funding Source: U.S. Department of Veterans Affairs. Full-text article
Evidence for psychiatric risks: - Suicide
◦ There’s moderate evidence [M] for a statistical association between cannabis use and suicidal ideation and suicide attempts (w/ higher incidence among heavy users), as well as ↑suicide completion incidence, per NAS.1
◦ Similarly, a meta-analysis found significantly ↑odds of suicide death w/ any cannabis use; however, in a VA-commissioned review2 of the meta-analysis, confidence in the results was limited, due to inconsistent findings and confounding among the studies.
◦ NIH3 also says marijuana use has been linked to suicidal thoughts but that study findings have been mixed. - Schizophrenia/Psychosis
◦ Substantial evidence [S] supports a statistical association between cannabis use and development of schizophrenia/other psychosis, w/ highest risk among most-frequent users.1
◦ Among psychotic d/o pts, there’s moderate evidence [M] for no statistical association between cannabis use and worsening negative sx (e.g., blunt affect); limited evidence [L] exists for a statistical association between cannabis use and ↑ in positive sx (e.g., hallucinations).1
◦ A VA-commissioned review2 found low-strength evidence of an association between cannabis use (THC, specifically) and psychotic sx development—both in populations at risk for psychotic disorders and average-risk pts—supporting, but not proving, the possibility of cannabis directly contributing to psychotic sx.
◦ A meta-regression analysis4 showed a significant positive association between THC dose and thought/perception disorders in adults ≥50 yo (association not present w/ THC-CBD combo). - Bipolar d/o
◦ Moderate evidence [M] for a statistical association between regular cannabis use and ↑mania/hypomania sx in bipolar pts1
◦ Limited evidence [L] for a statistical association between cannabis use and development of bipolar d/o, esp. among regular or daily users1
◦ A VA-commissioned review2 found low-strength evidence of an association between cannabis use and manic sx exacerbation in known bipolar dz, and higher incidence of new-onset mania in those w/o a bipolar dz dx. - Depression1
◦ Moderate evidence [M] for a statistical association between cannabis use and a small ↑risk for development of depressive disorders
◦ No evidence [I/N] for a statistical association between cannabis use and depressive d/o course change or sx change - Anxiety disorders1
◦ Limited evidence [L] for a statistical association between near-daily cannabis use and ↑anxiety sx
◦ Limited evidence [L] for a statistical association between cannabis use and development of any type of anxiety d/o, except social anxiety
◦ Social anxiety. Moderate evidence [M] supports a statistical association between regular cannabis use and ↑social anxiety d/o incidence.
◦ PTSD. Limited evidence [L] exists for a statistical association between cannabis use and ↑PTSD sx severity. There’s no evidence [I/N] for a statistical association between cannabis use and PTSD development.
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 VA 2017. Nugent SM, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. Primary Funding Source: U.S. Department of Veterans Affairs. Full-text article
3 NIDA 2019. Cannabis (Marijuana) DrugFacts. National Institute on Drug Abuse. Updated December 2019. Accessed July 23, 2024
4 Velayudhan L, et al. Evaluation of THC-Related Neuropsychiatric Symptoms Among Adults Aged 50 Years and Older: A Systematic Review and Metaregression Analysis. JAMA Netw Open. 2021 Feb;4(2):e2035913. Free, full-text article at PubMed® Central
Evidence for cognitive and social risks: - Cognitive domains
◦ Moderate evidence [M] supports a statistical association between impaired learning, memory, and attention and acute cannabis use, while evidence is limited [L] for a link between impairments in learning, memory, and attention and sustained abstinence from cannabis.1
◦ A VA-commissioned review2 also found moderate-strength evidence of an association between active, long-term cannabis use and small to moderate negative effects on cognitive fxn; evidence for cognitive effects of past use was insufficient.
◦ Among pts w/ psychotic disorders and hx of cannabis use, moderate evidence [M] supports a statistical association between cannabis use and better cognitive performance.1 - Academics/Education. Evidence is limited [L] for a statistical association between cannabis use and impaired academic achievement and education outcomes.1
- Social/Economic. Limited evidence [L] supports a statistical association between cannabis use and ↑unemployment, low income, or impaired social functioning/engagement in developmentally appropriate social roles.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 VA 2017. Nugent SM, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. Primary Funding Source: U.S. Department of Veterans Affairs. Full-text article
Pregnancy/Lactation-related risks Evidence for pregnancy/lactation-related risks: - Complications in birthing parent and fetus
◦ Evidence is incomplete, complicated by confounding use of other substances and reliance on self-reported data. Limited evidence [L] exists for a statistical association between cannabis smoking and pregnancy complications in the parent.1
◦ Marijuana shouldn’t be used for nausea during pregnancy; its use has been linked to lower birth wt and ↑risk of preterm birth and may affect fetal brain development.2 - Impaired fetal neurodevelopment. Certainty about specific effects is difficult, due to confounders in studies and data limitations; however, because of concerns about impaired neurodevelopment, ACOG3 encourages pregnant pts or those contemplating pregnancy to d/c marijuana use.
- Low-birth-wt offspring. Substantial evidence [S] supports a statistical association between cannabis smoking and lower-birth-wt offspring.1
- Infant NICU admission. Evidence is limited [L] for a statistical association between cannabis smoking and infant NICU admission.1
- Offspring: later outcomes. There’s insufficient/no evidence [I/N] for a statistical association between cannabis smoking and later outcomes in offspring (SIDS, cognition/academic achievement, later substance use).1
- Lactation. THC appears in breast milk, per limited data; because data on the effects of marijuana on infants are insufficient, ACOG discourages marijuana use while breastfeeding.3 NIH cautions that w/ regular marijuana use, the amount of THC in the breast milk may affect the baby’s brain development.2
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 NIDA 2019. Cannabis (Marijuana) DrugFacts. National Institute on Drug Abuse. Updated December 2019. Accessed July 23, 2024
3 ACOG 2017. Committee Opinion No. 722: Marijuana Use During Pregnancy and Lactation. Obstet Gynecol. 2017 Oct;130(4):e205-e209. Full-text article
Evidence for respiratory risks: - Respiratory sx1
◦ Substantial evidence [S] for a statistical association between long-term cannabis smoking and worse resp sx
◦ Moderate evidence [M] for a statistical association between cessation of cannabis smoking and improved resp sx - Asthma/COPD/Chronic bronchitis1
◦ Substantial evidence [S] for a statistical association between long-term cannabis smoking and more-frequent chronic bronchitis episodes
◦ Limited evidence [L] for a statistical association between occasional cannabis smoking and ↑COPD development, when controlled for tobacco use
◦ Insufficient/no evidence [I/N] for a statistical association between cannabis smoking and asthma development/exacerbations or COPD hospitalizations - Airway dynamics/Lung fxn
◦ Moderate evidence [M] for a statistical association between acute (but not chronic) cannabis smoking and improved airway dynamics1
◦ Moderate evidence [M] for a statistical association between cannabis smoking and higher FVC1
◦ Moderate-strength evidence suggests that low-level cannabis smoking doesn’t adversely affection lung fxn in young adults, over the course of about 2 decades; but some evidence suggests that daily use over an extended period may cause adverse pulmonary effects.2 - Lung CA
◦ There’s moderate evidence [M] for no statistical association between cannabis smoking and lung CA incidence, per NAS.1
◦ NCI3 notes conflicting evidence regarding CA risks.
◦ A VA-commissioned review2 found low-strength evidence for no association between light to moderate cannabis use and lung CA.
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 VA 2017. Nugent SM, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. Primary Funding Source: U.S. Department of Veterans Affairs. Full-text article
3 NCI 2024. Cannabis and Cannabinoids (PDQ®)–Health Professional Version. National Cancer Institute. Updated July 17, 2024. Accessed July 23, 2024
Infection & Immunity risks Evidence for infection and immunity risks:1 - HCV. Limited evidence [L] for no statistical association between daily cannabis use and liver fibrosis/hepatic dz in HCV pts.
- HIV. Insufficient/no evidence [I/N] for a statistical association between cannabis or dronabinol use and adverse immune status effects in HIV pts.
- HPV. Insufficient/no evidence [I/N] for a statistical association between regular cannabis use and ↑oral HPV incidence.
- Immunity in healthy individuals
◦ Limited evidence [L] for a statistical association between cannabis smoking and ↓inflammatory cytokine production
◦ Insufficient/no evidence [I/N] for a statistical association between cannabis smoking and other adverse immune cell responses
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
Cardiovascular, Cerebrovascular, & Metabolic risks Evidence for CV, cerebrovascular, and metabolic risks: - Cardiovascular/MI
◦ NAS1 found limited evidence [L] for a statistical association between cannabis smoking and the triggering of acute MI but no evidence [I/N] for a link between chronic effects of cannabis use and ↑acute MI.
◦ A VA-commissioned review2 found insufficient evidence for long-term CV event risk from cannabis use. - Cerebrovascular. Limited evidence [L] exists for a statistical association between cannabis use and ischemic stroke or subarachnoid hemorrhage.1
- Diabetes/Metabolic syndrome. Evidence is limited [L] for a statistical association between cannabis use and ↓metabolic syndrome risk, ↓diabetes risk, or ↑prediabetes risk.1
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 VA 2017. Nugent SM, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. Primary Funding Source: U.S. Department of Veterans Affairs. Full-text article
Evidence for CA risks. NCI1 notes conflicting evidence regarding risks of various CAs. - Lung CA. Moderate evidence [M] supports no statistical association between cannabis smoking and lung CA incidence, per NAS;2 a VA-commissioned review3 found low-strength evidence that light to moderate cannabis use isn’t assoc w/ lung CA.
- Head and neck CA. There’s moderate evidence [M] for no statistical association between cannabis use and head and neck CA incidence, per NAS.2 A VA-commissioned review3 found low-strength evidence that light to moderate cannabis use isn’t assoc w/ ↑head/neck CA risk.
- Testicular nonseminoma germ cell tumors. Limited evidence [L] exists for a statistical association between current, frequent, or chronic cannabis smoking and nonseminoma testicular germ cell tumor incidence, per NAS.2 A VA-commissioned review3 found the evidence for cannabis and testicular CA insufficient.
- Prostate/Cervical/Penile/Bladder/Anal CA. There’s insufficient/no evidence [I/N] for a statistical association between cannabis use and prostate, cervical, penile, bladder, or anal CA incidence, per NAS.2 A VA-commissioned review3 found the evidence for cannabis and transitional cell CA insufficient.
- Esophageal CA. Insufficient/no evidence [I/N] for a statistical association between cannabis smoking and esophageal CA incidence.2
- Malignant glioma. Insufficient/no evidence [I/N] for a statistical association between cannabis use and malignant glioma incidence.2
- NHL. Insufficient/no evidence [I/N] for a statistical association between cannabis use and NHL incidence.2
- Kaposi sarcoma. Insufficient/no evidence [I/N] for a statistical association between cannabis use and KS incidence.2
- CA in future offspring from parental use. There’s insufficient/no evidence [I/N] for a statistical association between parental cannabis use and subsequent incidence of AML/ALL/ANLL, rhabdomyosarcoma, astrocytoma, or neuroblastoma in offspring.2
Footnotes 1 NCI 2024. Cannabis and Cannabinoids (PDQ®)–Health Professional Version. National Cancer Institute. Updated July 17, 2024. Accessed July 23, 2024
2 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
3 VA 2017. Nugent SM, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. Primary Funding Source: U.S. Department of Veterans Affairs. Full-text article
Injury/Death-related risks Evidence for injury/death risks: - All-cause mortality. Insufficient/no evidence [I/N] for a statistical association between self-reported cannabis use and all-cause mortality.1
- Motor vehicle crashes
◦ Marijuana can slow reaction time, impair judgment of time and distance, and ↓ coordination, but its role in crashes is unclear.2
◦ Several studies have shown that drivers w/ THC in their blood were ~2x as likely to be responsible for a deadly crash or be killed than those who hadn’t used drugs or alcohol, but a large NHTSA study found no significant ↑crash risk traceable to marijuana after controlling for other factors.2
◦ However, substantial evidence [S] supports a statistical association between cannabis use and ↑risk of motor vehicle crashes, per NAS.1
◦ Also, a VA-commissioned review3 found moderate-strength evidence that acute cannabis intoxication is assoc w/ a moderate ↑ in collision risk. - Occupational accident/injury. Insufficient/no evidence [I/N] for a statistical association between general, nonmedical cannabis use and occupational accident/injury.1
- Overdose injuries/death1
◦ Moderate evidence [M] for a statistical association between cannabis use and overdose injury (e.g., pediatric resp distress, in states where cannabis is legal)
◦ Insufficient/no evidence [I/N] for a statistical association between cannabis use and cannabis-overdose death - Fall risk. A meta-regression analysis4 demonstrated a significant positive association between THC dose and dizziness/lightheadedness in adults ≥50 yo (association not present w/ THC-CBD combo).
Footnotes 1 NAS 2017. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. PDF
2 NIDA 2019. Drugged Driving DrugFacts. National Institute on Drug Abuse. Updated December 2019. Accessed July 23, 2024
3 VA 2017. Nugent SM, et al. The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Ann Intern Med. 2017 Sep 5;167(5):319-331. Primary Funding Source: U.S. Department of Veterans Affairs. Full-text article
4 Velayudhan L, et al. Evaluation of THC-Related Neuropsychiatric Symptoms Among Adults Aged 50 Years and Older: A Systematic Review and Metaregression Analysis. JAMA Netw Open. 2021 Feb;4(2):e2035913. Free, full-text article at PubMed® Central
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