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Cannabis

A widely used plant studied across pain, anxiety, sleep, and its interactions with mental health.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Cannabis, marijuana, THC, cannabidiol, CBD, then ranked by relevance.

The research indicates that cannabis use is associated with an increased risk of psychotic symptoms and disorders, with controlled laboratory studies showing that cannabinoid agonists can transiently produce schizophrenia-like symptoms in healthy individuals and exacerbate symptoms in those with schizophrenia. However, the evidence is complicated by high rates of polysubstance use, and the long-term effects and mechanisms remain areas of active investigation. The findings are consistent across multiple study types, but the overall confidence is limited by the prevalence of observational designs and the confounding factor of co-use with other substances.

Confidence in the evidence

Low-Moderate
  • The evidence includes controlled laboratory studies (RCTs) showing a causal link between cannabinoid agonists and transient psychotic symptoms, but these are acute effects and not necessarily indicative of long-term risk.
  • Observational and review studies consistently report an association between cannabis use and psychosis, but these are limited by confounding factors like polysubstance use and lack of blinding.
  • The sample sizes in the most direct experimental studies are not reported in the abstracts, and the overall body of evidence is heterogeneous in design and population.
  • There is a lack of large-scale, long-term prospective studies that adequately control for confounds, reducing the ability to draw firm causal conclusions.
How we rate confidence

Confidence reflects the strength of the underlying evidence, not whether the result is favorable. It weighs the number and size of studies, their design (randomized trials count for more than observational or single-case work), how consistently they point the same way, and their risk of bias.

Tiers run from Insufficient to High. High is rare in this field: small, early, or open-label studies land lower even when their direction is encouraging.

Evidence by study

Direction is each study's finding relative to your question: Supports, Opposes, No effect, Mixed, or Unclear.

Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. 2018
Unclear

This comprehensive review describes the ethnopharmacology and pharmacology of Cannabis sativa, including its key psychoactive constituent THC and the endocannabinoid system, but does not directly assess clinical outcomes.

review

Human Laboratory Studies on Cannabinoids and Psychosis. 2016
Supports

Controlled laboratory studies demonstrate that cannabinoid agonists produce positive, negative, and cognitive symptoms resembling schizophrenia in healthy subjects and transiently exacerbate symptoms in individuals with schizophrenia, challenging the self-medication hypothesis.

review of RCTs

Drug-Induced Psychosis: How to Avoid Star Gazing in Schizophrenia Research by Looking at More Obvious Sources of Light 2011
Supports

This review discusses evidence that cannabis, among other drugs, can induce schizophrenia-like psychosis, contributing to the view that liability to psychosis is continuously distributed in the population.

review

Substance-Induced Psychoses: An Updated Literature Review 2021
Supports

This updated review finds that abuse of cannabis plays a significant role in increasing the incidence of episodes resembling a psychotic disorder, though it notes the difficulty in distinguishing induced psychosis from primary psychotic disorders due to frequent comorbidity.

narrative review

Functional recovery trajectories in cannabis-induced first-episode psychosis: The role of dissociative symptoms in the discrepancy between symptomatic improvement and functional outcomes. 2026
Supports

In a 24-month prospective study of 72 patients with cannabis-induced first-episode psychosis, continued cannabis use was associated with worse functional outcomes, with dissociative symptoms mediating 35% of this effect.

prospective cohort · Sample size: 72

Drug models of schizophrenia. 2015
Unclear

This review selectively examines findings from cannabinoid pharmacological drug models to evaluate their similarity to schizophrenia, but does not provide a specific directional finding on cannabis itself.

review

A Clinical and Metabolic Study of Acute Intoxication with Cannabis Sativa and its Role in the Model Psychoses 1958
Unclear

This historical study describes the effects of oral cannabis administration and its potential as a model psychosis, but the abstract does not provide specific quantitative results.

clinical study

The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview 2006
Mixed

This review notes that cannabis use is a well-recognized risk factor for neuropsychiatric disorders and contributes to psychological problems in ecstasy users, but also that cannabinoids have neuroprotective actions that may partially block MDMA-induced neurotoxicity in animals.

review

MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress 2006
Mixed

This review states that around 90-95% of ecstasy/MDMA users also take cannabis, which can independently contribute to adverse neuropsychobiological profiles, though acute co-use may be interactive rather than additive due to cannabis's relaxant and hypothermic properties.

review

Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) 2000
Supports

This study raises concern that use of ecstasy, possibly in conjunction with cannabis, may lead to cognitive decline in otherwise healthy young people, suggesting an impairment of working memory.

observational

Patterns of simultaneous polysubstance use in drug using university students 2006
Unclear

This study found that cannabis is frequently co-administered with alcohol, tobacco, and other substances, but patterns of cannabis use were not systematically related to other substances administered.

observational · Sample size: 149

Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. 2012
Unclear

This review discusses synthetic cannabinoids (e.g., K2, Spice) as herbal marijuana alternatives, noting their adverse effects ranging from minimal to life-threatening, but does not directly address cannabis itself.

review

Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). 2010
Unclear

This in vitro study found that THC inhibits human P-glycoprotein and breast cancer resistance protein in a concentration-dependent manner, suggesting potential drug-drug interactions, but does not assess clinical outcomes.

in vitro

Medicinal Plants with Psychoactive Properties: A Comprehensive Review 2026
Unclear

This review includes Cannabis sativa among 20 medicinal plants with psychoactive properties, noting its neuropharmacological activities through modulation of the endocannabinoid system, but does not provide specific clinical findings.

review

Cannabis Sativa, religion and society: Historical, medicinal, legal, and sacramental perspectives 2026
Unclear

This article examines the historical, medicinal, legal, and religious aspects of Cannabis sativa, but does not present empirical findings on health outcomes.

review

Prophylactic efficacy of cannabidiol and sodium nitroprusside in a ketamine model of schizophrenia: sex-dependent effects on positive-like and cognitive impairments 2026
Mixed

In a rodent model of schizophrenia, cannabidiol (CBD) combined with sodium nitroprusside showed prophylactic efficacy in preventing ketamine-induced positive-like and cognitive impairments, with sex-dependent effects, but CBD alone had limited efficacy.

preclinical (animal study)

Psychedelic-Assisted Psychotherapy for the Treatment of PTSD: A Systematic Review and Meta-Analysis 2026
No effect

In a meta-analysis of 11 RCTs for PTSD, a single cannabidiol trial showed no clear benefit, while MDMA-assisted psychotherapy showed a significant moderate-to-large reduction in PTSD symptom severity.

systematic review and meta-analysis · Sample size: 358

Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada 2013
Unclear

This study found that ayahuasca-assisted therapy was associated with improvements in factors related to problematic substance use, but does not directly address cannabis.

observational

Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey 2020
Unclear

This survey found persisting reductions in cannabis, opioid, and stimulant misuse after naturalistic psychedelic use, but the cross-sectional design cannot determine causality.

cross-sectional survey

Standardised Mindfulness-Based Interventions in Healthcare: An Overview of Systematic Reviews and Meta-Analyses of RCTs 2015
Unclear

This review found that mindfulness-based interventions improved depressive symptoms, anxiety, stress, quality of life, and physical functioning, but does not address cannabis.

systematic review and meta-analysis · Sample size: 8683

A cross-national comparison of nonmedical and medical use of psychedelic drugs in the international cannabis policy study. 2026
Unclear

This study estimated prevalence of psychedelic use and medical discussions, but does not directly address cannabis.

cross-sectional survey

The need for another tool: Australian healthcare professionals on the use of psilocybin for existential distress in people with cancer 2026
Unclear

This qualitative study explored healthcare professionals' attitudes toward psilocybin-assisted therapy for existential distress in cancer patients, but does not address cannabis.

qualitative · Sample size: 11

Past-Year Psilocybin and Alcohol Co-Use: Associations With Mental Health Symptoms 2026
Unclear

This study found that individuals with past-year psilocybin and alcohol co-use had fewer depressive symptoms than those who used alcohol without psilocybin, but does not directly address cannabis.

cross-sectional survey · Sample size: 2841

Attitudes of Mental Healthcare Professionals Towards the Use of Psychedelics in the Treatment of Substance Use Disorders: A Systematic Review 2026
Unclear

This systematic review found that mental healthcare professionals hold cautiously optimistic attitudes toward psychedelic-assisted therapy for substance use disorders, but does not directly address cannabis.

systematic review · Sample size: 966

Spiritual health and healing in Ethiopia: A scoping review and thematic analysis of beliefs, practices, and gaps in healthcare integration 2026
Unclear

This scoping review maps spiritual health beliefs and practices in Ethiopia, but does not address cannabis.

scoping review

Points of agreement

  • Multiple reviews and controlled laboratory studies converge on the finding that cannabinoid agonists can induce transient psychotic-like symptoms in healthy individuals and exacerbate symptoms in those with schizophrenia.
  • Observational studies consistently report an association between cannabis use and increased risk of psychotic disorders, though causality is difficult to establish due to confounding factors.
  • The evidence suggests that cannabis use is a significant environmental factor in the development of psychosis, particularly in vulnerable individuals.

Conflicts

  • There is a conflict between the potential neuroprotective effects of cannabinoids (e.g., blocking MDMA-induced neurotoxicity in animal studies) and the observed adverse neuropsychiatric effects in human observational studies.
  • The role of cannabis in cognitive decline is debated, with some studies suggesting impairment while others note that effects may be confounded by polysubstance use.
  • The self-medication hypothesis for cannabis use in schizophrenia is challenged by laboratory studies showing exacerbation of symptoms, but observational data cannot fully rule it out.

Gaps

  • Long-term prospective studies with adequate control for polysubstance use are lacking, making it difficult to isolate the specific effects of cannabis on psychosis and cognition.
  • The durability of cannabis-induced psychotic symptoms and the long-term functional outcomes in patients with cannabis-induced psychosis are not well characterized.
  • There is a need for more research on the dose-response relationship and the differential effects of various cannabinoids (e.g., THC vs. CBD) on mental health outcomes.
  • The role of genetic vulnerability (e.g., COMT, DAT1 polymorphisms) in moderating the effects of cannabis on psychosis is underexplored in large-scale studies.
  • Most studies focus on acute or short-term effects; the long-term neurobiological and cognitive consequences of chronic cannabis use remain poorly understood.
Browse these studies in the library
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Cannabis, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when Cannabis or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

Ask your own question in the Research Synthesis Tool

623 articles · 180 from the last two years · 2,747,900 participants across 252 studies reporting sample size

Common study designs

review 101 systematic review 26 observational cohort 42 cross-sectional survey 47 theoretical or philosophical paper 32

Research

Synthesize the evidence → Search all →

Legalizing Magic Mushrooms: A Different Set of Laws for a Different Kind of Drug

Edward S. Adams

This article examines how the cannabis industry is regulated, tracing its origins, history, and flaws. It then compares the cannabis and psilocybin industries, arguing that the cannabis regulatory model should not be copied for psilocybin. Instead, the author proposes customized regulatory approaches that address psilocybin's distinct features, aiming to create a safe, effective, and well-regulated market.

DOI: 10.2139/ssrn.7094518

Unveiling the Sacred Plant: Reidentifying Soma, Haoma, and the Assyrian Sacred Tree

Milind Raskar

A multidisciplinary investigation combining textual analysis, fieldwork in India's Kutch region, and comparative ethnobotany identifies Vernonia cinerascens Sch. Bip. as a strong candidate for the sacred Soma plant of the Rigveda and its Iranian counterpart Haoma. The plant's woody stems, arrow-like shoots, tawny color, and leafy sprigs match ancient descriptions. Pressing its branches yielded a golden-tawny juice with a crackling sound noted in hymns. Experiential trials reported psychoactive and healing effects—relaxation, enhanced concentration, pain relief, calm joy—similar to those praised in the texts. The plant's known medicinal uses in African ethnobotany for mental disorders and depression further support the identification. Comparisons with Assyrian sacred tree iconography and Zoroastrian Barsom ritual suggest a broader Near Eastern continuity of sacred plant traditions.

DOI: 10.31235/osf.io/5sxaq_v1

The FDA Backdoor to MDMA Rescheduling

SSRN Electronic Journal • Vincent Joralemon

The Drug Enforcement Administration (DEA) classifies MDMA as a Schedule I controlled substance, the most restrictive category under the Controlled Substances Act. However, Lykos Therapeutics (formerly MAPS PBC) has submitted a New Drug Application for MDMA-assisted therapy for PTSD. If the FDA approves this drug, it would provide the 'accepted medical use' that Schedule I drugs are statutorily denied, triggering a rescheduling process. Based on precedents like XYWAV and cannabis-derived medications, the DEA would likely reschedule only the specific FDA-approved drug product—likely to be marketed as RENSANSE—to Schedule II or III, while raw MDMA remains on Schedule I. This mechanism offers a model for incrementally relaxing federal restrictions on psychedelic substances and expanding research access.

DOI: 10.2139/ssrn.6960838

Regulating Psilocybin as Food, Not Drugs

Julia Etkin, Vincent Joralemon

Psilocybin, currently a Schedule I controlled substance with no accepted medical use and high abuse potential, is actually among the safest psychoactive compounds by comparative-harm metrics—far safer than alcohol and tobacco, which are exempt from the Controlled Substances Act and regulated as adult-use commodities. This essay argues that psilocybin should be regulated under food law, specifically the dietary-supplement framework of the Dietary Supplement Health and Education Act of 1994, rather than drug law.

DOI: 10.2139/ssrn.6960858

Functional recovery trajectories in cannabis-induced first-episode psychosis: The role of dissociative symptoms in the discrepancy between symptomatic improvement and functional outcomes.

Psychiatry research • September 1, 2026 • Valerio Ricci, Andrea Paggi, Giovanni Martinotti et al.

In patients with cannabis-induced first-episode psychosis, dissociative symptoms—especially depersonalization and derealization—are strong independent predictors of poor functional recovery over 24 months. Among 72 patients, three recovery trajectories emerged: Rapid Recovery (34.7%, GAF +29.1 points), Gradual Recovery (40.3%, GAF +15.7 points), and Persistent Impairment (25.0%, GAF +4.7 points). A symptom-function discrepancy occurred in 31.9% of patients, where psychotic symptoms improved but functioning did not; these patients had higher baseline dissociation scores (33.8 vs. 18.1). Dissociation mediated 35% of cannabis's negative effect on functional outcomes. A high-risk subgroup (22%) with elevated dissociation, depression, and continued cannabis use showed minimal improvement despite treatment. Routine dissociation assessment and targeted interventions may improve outcomes.

DOI: 10.1016/j.psychres.2026.117240 Full text Cannabis-induced psychosis Depersonalization Dissociation First-episode psychosis +1

A cross-national comparison of nonmedical and medical use of psychedelic drugs in the international cannabis policy study.

The International journal on drug policy • August 1, 2026 • Myfanwy Graham, Yimin Ge, Rosalie Liccardo Pacula et al. • 1 citation

An estimated 19% of adults in Canada, the United States, Australia, and New Zealand have used psilocybin, LSD, MDMA, or ketamine at some point in their lives. Psilocybin was the most commonly used substance, with lifetime use highest in Canada (16.3%), followed by the US (13.0%) and New Zealand (12.1%), and lowest in Australia (7.8%). Among those who had ever used a psychedelic, 10-20% had asked their medical provider about medical use, and over a third of past-year users reported experiencing an adverse health effect. Past-month use was low across all countries. Consumer interest in therapeutic use has outpaced clinical trials and therapeutic provisions, and many people use these substances outside regulated pathways, which may increase the risk of adverse events.

DOI: 10.1016/j.drugpo.2026.105348 Full text Adverse events Drug policy Nonmedical use Psychedelics

Medicinal Plants with Psychoactive Properties: A Comprehensive Review

Sciences of Phytochemistry • July 12, 2026 • Fakhray Rimi, Jannatul Fardous, Fahmida Zaman et al.

A review of twenty psychoactive medicinal plants, including Withania somnifera, Cannabis sativa, Valeriana officinalis, Psilocybe cubensis, and Passiflora incarnata, finds they contain alkaloids, flavonoids, terpenoids, and cannabinoids that modulate serotonergic, dopaminergic, GABAergic, and endocannabinoid systems. These plants show anxiolytic, antidepressant, sedative, hallucinogenic, or cognition-enhancing effects in preclinical and limited clinical studies, along with antioxidant, anti-inflammatory, neuroprotective, and adaptogenic properties. However, most evidence remains preclinical, with limited clinical validation of efficacy, safety, standardization, and long-term use, underscoring the need for further experimental and clinical investigations.

DOI: 10.58920/sciphy0502612 Medicinal plants Phytochemical Neurochemical Synthetic cannabinoids +3

Psychedelics stores, their regulation and public health: knowledge, perceptions, attitudes and opinions of Canadians.

The International journal on drug policy • July 9, 2026 • François Gagnon, Anne Philibert, Benjamin Carignan et al.

Most Canadian adults are unfamiliar with the proliferation of illegal psychedelic retail stores selling psilocybin, DMT, and related substances, with 79.1% unaware of the stores and 80.3% unaware of the products sold. Among those with some familiarity, perceptions of risks and benefits coexist, with ambivalence being the most common stance. Respondents were equally divided between closing the stores and maintaining the current unregulated status quo. However, 66.6% supported authorizing sales under a regulatory framework, even among those with no direct exposure to psychedelics. Large majorities favored public health protections over fiscal considerations, product restrictions, promotion limits, and caps on store numbers. Public support for legal regulation appears receptive but not fixed, potentially shaped by the regulatory framework's features.

DOI: 10.1016/j.drugpo.2026.105427 Full text Attitudes Knowledge Opinions Psychedelics stores +2

Reducing Research Harms: Analysis and Recommendations for Researching Schedule I Substances Under the HALT Fentanyl Act

Journal of Science Policy & Governance • July 2, 2026 • Alaina M. Jaster, Joseph J. Hennessey, Tanner L. Anderson et al.

Research on Schedule I substances in the United States is heavily restricted by the Controlled Substances Act, creating what is termed Research Harm—the restriction or deterrence of legitimate scientific inquiry due to governmental regulatory controls and criminal prohibitions. Barriers include lengthy DEA registration timelines, inconsistent guidance, and policy confusion, limiting access to substances with therapeutic potential like psilocybin, MDMA, cannabis, and DOI. The 2025 HALT Fentanyl Act introduces procedural improvements such as expedited registration and shared institutional access but leaves key regulatory issues unresolved. Recommended reforms include revising medical utility interpretations, conducting periodic evidence reviews, and establishing a scheduling framework for easier research access.

DOI: 10.38126/jspg280109 Sanctions Confusion Controlled substance Schedule +8

Past-Year Psilocybin and Alcohol Co-Use: Associations With Mental Health Symptoms

Journal of Drug Issues • July 1, 2026 • Haley M Hummel, Alexia N Obrochta, David C. R. Kerr et al.

People who used both psilocybin and alcohol in the past year reported fewer depressive symptoms compared to those who used alcohol without psilocybin, based on a nationally representative U.S. survey. The analysis adjusted for age, sex, race, ethnicity, survey period, and other substance use. When cannabis and other psychedelic use were not accounted for, psilocybin use was also linked to lower anxiety symptoms. Because the study was observational and relied on self-reports, it cannot show cause and effect. The findings suggest potential mental health benefits of psilocybin when used alongside alcohol, but experimental and long-term studies are needed to confirm.

DOI: 10.1177/00220426261466154 Psilocybin Anxiety Hallucinogen Mental health +10

Clinical trials

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