The Behavioral Sequelae of Cannabis Use in Healthy People: A Systematic Review
Open accessAbstract
Background: Cannabis is known to have a broad range of effects on behavior, including experiencing a “high” and tranquility/relaxation. However, there are several adverse behavioral sequalae that can arise from cannabis use, depending on frequency of use, potency (e.g., THC content), age of onset, and cumulative exposure. This systematic review examined evidence for cannabis-related adverse behavioral sequalae in otherwise healthy human subjects. Methods: Following PRISMA guidelines, we conducted a systematic review of cross-sectional and longitudinal studies from 1990 to 2020 that identified cannabis-related adverse behavioral outcomes in subjects without psychiatric and medical co-morbidities from PubMed and PsychInfo searches. Key search terms included “cannabis” OR “tetrahydrocannabinol” OR “cannabidiol” OR “marijuana” AND “anxiety” OR “depression” OR “psychosis” OR “schizophrenia” “OR “IQ” OR “memory” OR “attention” OR “impulsivity” OR “cognition” OR “education” OR “occupation”. Results: Our search detected a total of 2,870 studies, from which we extracted 124 relevant studies from the literature on cannabis effects in the non-clinical population. Effects of cannabis on several behavioral sequelae including cognition, motivation, impulsivity, mood, anxiety, psychosis intelligence, and psychosocial functioning were identified. The preponderance of the evidence suggests that frequency of cannabis use, THC (but not CBD) content, age of onset, and cumulative cannabis exposure can all contribute to these adverse outcomes in individuals without a pre-existing medical condition or psychiatric disorder. The strongest evidence for the negative effects of cannabis are for psychosis and psychosocial functioning. Conclusions: Although more research is needed to determine risk factors for development of adverse behavioral sequelae of cannabis use, these findings underline the importance of understanding vulnerability to the adverse effects of cannabis, which has implications for prevention and treatment of problematic cannabis use.
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Heavy cannabis use by youth and young adults predicts an increased risk of major depression.
“Regular cannabis use is associated with more depressive symptoms, and heavy cannabis use by youth and young adults predicts an increased risk of major depression [41]; twofold for cannabis misusers and threefold to fivefold for people with a CUD [42].”
From Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits (2025) · cites this paper as [41]
The Results > Depression section reports that six longitudinal studies identified heavy or chronic adolescent cannabis use as a risk factor for depression in adulthood. The Results table also describes evidence for a later major depressive disorder diagnosis, but the review characterizes the overall evidence as mixed and does not establish the same prediction for heavy use beginning in young adulthood. No page numbers were available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredRegular cannabis use is associated with more depressive symptoms.
“Regular cannabis use is associated with more depressive symptoms, and heavy cannabis use by youth and young adults predicts an increased risk of major depression [41]; twofold for cannabis misusers and threefold to fivefold for people with a CUD [42].”
From Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits (2025) · cites this paper as [41]
The Results (Depression) report that three cross-sectional studies found more severe depressive symptoms in cannabis users than non-users. But the Results and Discussion describe the overall evidence as mixed, with some studies finding no association after accounting for confounders. The unqualified claim overstates that evidence. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRegular cannabis use is associated with anxiety symptoms.
“Regular cannabis use is associated with anxiety symptoms [41] and increased risk of anxiety disorders particularly during the withdrawal stage [43].”
From Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits (2025) · cites this paper as [41]
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“Regular cannabis use is associated with more depressive symptoms, and heavy cannabis use by youth and young adults predicts an increased risk of major depression [41]; twofold for cannabis misusers and threefold to fivefold for people with a CUD [42].”
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Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome
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Down and High: Reflections Regarding Depression and Cannabis
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Pedrazzi, J. F. C., Ferreira, F. R., Silva-Amaral, D., Lima, D. D. A., Hallak, J. E. C., Zuardi, A. W., Bel, E. A. D., Guimarães, F. S., Costa, K. C. M., Campos, A. C., et al. (2022) · Psychopharmacology · doi:10.1007/s00213-022-06196-4 · Cited by 52 · see citing works
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Self-citationKozak, K., Smith, P. H., Lowe, D. J. E., Weinberger, A. H., Cooper, Z. D., Rabin, R. A., & George, T. P. (2021) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2021.1946071 · Cited by 38 · see citing works
Self-citationAndrews, C. N., Rehak, R., Woo, M. M. K., Walker, I. O., Ma, C., Forbes, N., Rittenbach, K., Hathaway, J., Wilsack, L., Liu, A., et al. (2022) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.17265 · Cited by 31 · see citing works
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Hasbi, A., Madras, B. K., & George, S. R. (2022) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2022.07.003 · Cited by 15 · see citing works
Sorkhou, M., Johnstone, S., Kivlichan, A. E., Castle, D. J., & George, T. P. (2022) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2022.2118060 · Cited by 14 · see citing works
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Cannabis use following bariatric surgery is associated with anxiety and maladaptive eating
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- Authors
- Sorkhou, M., Bedder, R. H., & George, T. P.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- Toronto Metropolitan University (CA)
- Corresponding author
- George, Tony P.
- Venue
- Frontiers in Psychiatry
- Publisher
- Frontiers Media SA
- Published
- 2021-02-16
- Volume
- 12
- Pages
- 630247-630247
- ISSN
- 1664-0640 (ISSN-L)
- PMC
- PMC7920961
- OpenAlex
- W3131607900
- Cited by
- 61
- References
- 183
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 15 · 2023: 13 · 2022: 10 · 2021: 4 · 2013: 1
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- cannabis use, psychosis, psychosocial functioning, cognitive impairment, impulsivity, anxiety, depression, tetrahydrocannabinol, cannabidiol, age of onset, motivation, IQ, attention, problematic cannabis use
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