European Archives of Psychiatry and Clinical Neuroscience (2025) 275:281–292

https://doi.org/10.1007/s00406-024-01880-2

INVITED REVIEW

Cannabis, cannabinoids and health: a review of evidence on risks

and medical benefits
E. Hoch1,2,3 · N. D. Volkow4 · C. M. Friemel2 · V. Lorenzetti5 · T. P. Freeman6 · W. Hall7,8

Received: 20 February 2024 / Accepted: 13 August 2024 / Published online: 19 September 2024
© The Author(s) 2024

Abstract
The legalization of cannabis for medical and recreational purposes has progressed internationally. Cannabis and cannabi-
noids are advocated for a plethora of medical indications. An increasing number of medical and nonmedical users regularly
consume large doses of delta-9-Tetrahydrocannabinol (THC), the main active component of cannabis. Aim: to summarize
the evidence on (1) risks of recreational cannabis use and (2) effectiveness and safety of medicinal cannabis. Findings on
recreational use: Cannabis is mostly used to experience its acute rewarding effects. Regular use of high THC products can
produce addiction (cannabis use disorder or CUD). Acute consumption of high THC doses (including unintentionally) can
cause time-limited mental, gastrointestinal, and cardiovascular problems and motor vehicle accidents. Chronic patterns of
cannabis use have been associated with multiple adverse outcomes that are of particular concern among adolescents and
young adults, such as, disrupted learning, impaired cognitive performance, reduced educational attainment and an increased
risk of CUD, psychosis/schizophrenia, mood and anxiety disorders and suicidal behaviors. There is debate about the extent
to which cannabis use is a cause of these adverse outcomes. Physical health risks (e.g., respiratory and cardiovascular, pre-
maturity and restricted fetal growth, hyperemesis syndrome among others) have also been linked with repeated consump-
tion of cannabis with a high THC content. Findings on medical cannabis use: Herbal cannabis, medicines from extracted or
synthetized cannabinoids—often used as adjuvants to standard medicines—may produce small to modest benefits. This is
primarily the case in treating chronic pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and refractory
epilepsy (in the case of cannabidiol, CBD). The evidence is inconclusive on their value in treating mental disorders and
other medical conditions. Safety: Cannabis-based medicine is generally well tolerated. There is a risk of mild to moderate
adverse effects and CUD.

Keywords Cannabis*/adverse effects · Cannabinoids*/therapeutic use · Humans · Medical Marijuana* · Marijuana abuse ·
Public health

6
* E. Hoch Addiction and Mental Health Group, Department
[email protected] of Psychology, University of Bath, Bath, UK
7
1 National Centre for Youth Substance Use Research, Faculty
Department of Psychiatry and Psychotherapy, LMU
of Health and Behavioural Sciences, The University
University Hospital, LMU Munich, Munich, Germany
of Queensland, Brisbane, Queensland, Australia
2
IFT Institut für Therapieforschung, Centre for Mental Health 8
Queensland Alliance for Environmental Health Sciences,
and Addiction Research, Munich, Germany
Faculty of Health and Behavioural Sciences, The University
3
Department Clinical Psychology and Psychotherapy, of Queensland, Brisbane, Queensland, Australia
Charlotte Fresenius University, Munich, Germany
4
National Institute on Alcohol Abuse and Alcoholism,
Bethesda, Maryland, USA
5
Neuroscience of Addiction and Mental Health Program,
School of Behavioural and Health Sciences, Faculty
of Health Science, Australian Catholic University,
Melbourne, Victoria 3065, Australia

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282 European Archives of Psychiatry and Clinical Neuroscience (2025) 275:281–292

Introduction Methods

In 2021, the UNODC estimated that 219 million people, This work aims to update a large systematic literature
4.3% of the global adult population, had used cannabis [1]. research on “benefits and risks of cannabinoids” commis-
Its nonmedical use has been prohibited under international sioned by the German Ministry of Health [14–18]. For
drug control treaties since 1961. Cannabis consumption this reason, we conducted a selective literature research in
remains the highest in North America, where 17.4% of the PubMed and the Cochrane Central Register of Clinical Tri-
population aged between 15 and 64 used it in the past year als. The search period was from 10.5.2016 to 10.5.2023.
[2]. Prevalence rates are lower in Oceania (12.2%), West and PubMed was searched with combinations of the mesh terms
Central Africa (9.7%) and Europe (7.8%) [2] with consider- “Cannabis” or “Cannabinoid” or “Marijuana” or “Medical
able variations between countries within these regions. The Marihuana” or “Medical cannabis” or “Pharmaceutical
past 25 years have seen different policies towards cannabis cannabis”. Our search procedure gave priority to systematic
use for medical or recreational purposes [3]. In the United reviews and meta-analyses of research on cannabis and can-
States and Canada cannabis legalization has been accompa- nabinoids, published in the past decade. In their absence,
nied by increases in the number of regular users who con- we included studies with the strongest research designs that
sume increasingly higher doses of tetrahydrocannabinol (the had adequate statistical power and have been published since
main psychoactive ingredient in cannabis) [4, 5]. The higher the most recent review. The references of the studies found
potency of cannabis products [6], diverse cannabis formula- were also screened to identify further relevant studies. We
tions and modes of administration (e.g., edibles, beverages, used the approach to causal inference outlined in Text Box 1.
vaping, and dabbing) have raised concerns about the adverse
public health impacts of cannabis legalization particularly
when there is little or no regulatory oversight [7]. Results
We have also seen a rapid development in the basic sci-
ence of cannabinoids, including characterization and func- Risks of recreational cannabis use
tion of the endocannabinoid system (ECS) in the human
brain and other organs, the pharmacology of cannabinoids, Acute effects may occur shortly after a single occasion or
and therapeutic cannabinoid development [8]. Growing evi- infrequent cannabis use. Chronic use is defined as daily or
dence indicates that dysregulation of ECS may contribute near daily use over months or longer.
to brain dysfunction, psychopathology, neurodevelopmental
problems, neurodegenerative diseases, neuroinflammation, Reinforcing effects
among other physiological functions [9, 10]. The last decade
has also seen a significant increase in scientific literature Cannabis is used recreationally because of its rewarding
addressing the effects of cannabis and cannabinoids for rec- effects that are associated with decreased stress reactivity
reational and medicinal purposes [11–13]. and an enhanced sense of well-being [11]. Rewarding affects
To guide policies regarding access and oversight for can- can include positive effects e.g., euphoria and the relief of
nabis for recreational of medicinal purposes it is crucial to adverse experiences such as anxiety. These rewarding effects
summarize the literature on the risks for recreational use are linked with the agonist effects of THC at the cannabinoid
and its therapeutic benefits. In this review we summarize (1) CB1 receptor that drive THC’s modulation of dopaminer-
mental, physical, and social risks of cannabis when used as gic signaling in the nucleus accumbens, the main reward
recreational drug and (2) the efficacy and safety of cannabis- center in brain. The anxiolytic effects of cannabis are medi-
based medicines. ated both by THC and cannabidiol (CBD) in part through

Text Box 1  Approach to causal inferences [19]

In assessing whether cannabis was a cause of an adverse health effect we assessed

1. Evidence of an association between cannabis use and the health outcome
2. Evidence that reverse causation was an implausible explanation of the association from experiments (when ethically acceptable) and otherwise
from prospective studies
3. Evidence that the association was not explained by uncontrolled and unmeasured factors, e.g., by statistical analyses controlling for confound-
ing variables
4. Evidence that a causal relationship between cannabis use and the health outcome was biologically plausible from animal or human experi-
ments, the neurobiology of the cannabinoid system and the pathophysiology of the health outcome
European Archives of Psychiatry and Clinical Neuroscience (2025) 275:281–292 283

their effects in the amygdala. The doses of THC and routes learning, global cognition, memory and cognitive impulsiv-
of administration determine the magnitude of its reward- ity [26, 27]. There is emerging evidence for decrements in
ing and anxiolytic effects. Other neurotransmitter systems, specific memory components (i.e., verbal, encoding, epi-
neuromodulators and individual metabolism differences also sodic and prospective), visual recognition and attentional
account for large differences in the effects of cannabis. At bias [26, 27]. Other cognitive domains that were inconsist-
high THC doses, acute cannabis intoxication can produce ently impaired include attention, executive function/abstrac-
unpleasant feelings (e.g. irritability, anxiety), distorted per- tion, working memory/updating, psychomotor function,
ceptions (e.g. paranoid thoughts, short-lived hallucinations, decision making, verbal/language, processing speed, verbal
delusions or depersonalization) and dysfunctional behavior fluency, and other memory components [26, 27]. There were
[20, 21]. Overdosing and unintentional cannabis use may no differences in simple reaction time, visuospatial learning,
cause short term psychiatric, gastrointestinal, and cardiovas- visual immediate memory, recognition, attention (sustained,
cular problems in children, teens, and adults [22, 23]. These divided) and time estimation [26, 27]. There is preliminary
unpleasant symptoms generally subside without the need evidence of cognitive impulsivity and poorer verbal memory
for medical assistance but can require medical assistance in and visual recognition in older studies of recreational users
more severe cases. [28].
Cognitive alterations in cannabis users appear to improve
Motoric incoordination with abstinence. For example, when abstinence lasted longer
than 42 h, 72 h and 25 days, cognitive function improved in
Acute cannabis consumption has consistently been associ- most domains [26, 29]. Impairments that were more persis-
ated with a modest increase in the risk of traffic accidents, tent after abstinence in some studies included impulsivity,
with odd ratios ranging from 1.25 to 1.97 [17]. Measuring verbal memory and fluency, working memory, performance
THC-related impairment and fitness to drive is more com- in other memory domains; learning; attention, executive
plicated than for alcohol because the absorption and bio- function and psychomotor function.
availability of THC does not follow a uniform time- and Cognitive performance was generally not affected by age,
dose-dependent course and cannabis-related behavioral although cognitive impairments were worse in older people
impairments differ from those of alcohol [24]. Thus, there with psychosis (e.g., cognitive impulsivity, verbal memory,
are no reliable cut-off values for blood THC levels that indi- visual recognition) [28]. There is mixed evidence on the
cate when an individual is impaired. Orally administered effects of the age of first cannabis use and duration of use on
cannabis produces a protracted increase in blood THC con- cognitive performance, except for IQ, which decreased by
centration and prolongs impaired driving performance com- 2 points each year after the start of frequent/dependent use
pared to inhaled cannabis. Frequent cannabis users may be [30]. Emerging evidence indicates that heavier use, higher
less impaired because they may show tolerance to the motor doses and higher frequency of cannabis use adversely affect
incoordination and cognitive disruptive effects of cannabis. cognition [26, 29].
Recovery of driving-related skills appears to occur 5–6 h
after cannabis intoxication but individuals may vary in the Motivation
amount and duration of impairment [24]. The concurrent use
of cannabis and alcohol produces greater driving impairment There is partial support from longitudinal studies for a
than cannabis alone [25]. causal link between cannabis use and a reduction in motiva-
tion, that has been referred to as an “a motivation syndrome”
Cognition [31]. It manifests as a reduce motivation to engage in every-
day activities such as a diminished desire to study or work,
Acute intoxication with cannabis and cannabinoids (THC, engage in social or recreational activities people who use
THC/CBD extracts) increases disinhibition, and impairs ver- cannabis frequently [32]. A lack in motivation may also be
bal memory, other memory components, learning, attention, related to decreased reward sensitivity. Mainly driven by
attentional bias, and psychomotor function [26, 27]. Acute striatal dysfunction in the brain, disrupted reward processing
intoxication has inconsistent effects on working memory, is a key characteristic in multiple types of addiction [33].
verbal fluency, executive function and time estimation.
Most of these effects recover within hours or a cou- Psychosocial consequences
ple of days but they can persist for longer time periods in
chronic cannabis users. In non-intoxicated, current canna- Early onset of cannabis use (<15 years of age) and fre-
bis users, impaired cognitive performance shows small-to- quent use in early adolescence are associated with lower
medium effect sizes [26, 27]. The domains most consist- educational achievement [34–36]. Low educational success
ently adversely affected are forgetting (retrieval/recall) and includes early school dropout, lower rates of participation
284 European Archives of Psychiatry and Clinical Neuroscience (2025) 275:281–292

in university education and fewer academic degrees. Edu- between this risk and the frequency of cannabis use [16].
cational success is negatively associated with the age onset A multinational study in Europe and Brazil [50] found that
of cannabis use. There are inconsistent and limited data on daily use of high potency cannabis increased the risk of psy-
antisocial behavior and psychosocial harm (e.g., family, pro- chosis fivefold compared to non-users while daily use of
fessional and economic problems) [34]. The risk of physical low potency cannabis doubled the risk. Use less than once
violence is increased in regular cannabis users, especially in a week was not associated with a psychotic disorder risk
those with severe mental disorders [37, 38]. Risk of physical (other than acute psychoses which can emerge even with
dating violence, victimization and perpetration is increased first time consumption of high THC doses). The prevalence
in female adolescent cannabis users and higher among alco- of daily cannabis use and high potency cannabis use was
hol users [39]. positively associated with the incidence of treated psycho-
sis across study sites in Europe and Brazil. More recently,
Mood and anxiety disorders a study based on electronic record over 5 decades in the
Danish population reported an increase in the incidence of
Research is showing that there are some individuals who schizophrenia associated with use of THC and CUD, pre-
use cannabis to reduce symptoms of mood or anxiety dis- dominantly among young males 20–30 years of age in whom
orders [40]. Regular cannabis use is associated with more cannabis use accounted for 30% of the cases [51].
depressive symptoms, and heavy cannabis use by youth and Triangulation of evidence from genetically sensitive
young adults predicts an increased risk of major depression research designs [52] indicates that the observed associa-
[41]; twofold for cannabis misusers and threefold to fivefold tion may reflect in part a causal effect of cannabis use on
for people with a CUD [42]. Regular cannabis use is asso- schizophrenia. The risks of cannabis use are more severe
ciated with anxiety symptoms [41] and increased risk of for people who have psychotic disorders. In the laboratory,
anxiety disorders particularly during the withdrawal stage administration of THC increases psychotic symptoms in
[43]. Emerging evidence found a non-significant association people with schizophrenia [53]. A meta-analysis of longi-
between chronic cannabis consumption and social anxiety tudinal studies [54] found that continued cannabis use in
disorders [44, 45] and another study showed that cannabis people with psychosis is associated with an increased risk
use did not impede recovery from panic disorder’ when of relapse to psychosis and with longer hospital stays than
treated with other medications or treatments [46]. Risk of in non-users [55].
anxiety disorders is twofold higher in people who misuse
cannabis, threefold to fourfold higher in those with a CUD Cannabis use disorder (CUD)
[42, 45]. Associations between cannabis use and depressive
or anxiety disorders were mixed in the reviewed studies, and CUD refers to clinically significant impairment or distress
weaker when analyses account for study quality, a diagnosis associated with repeated cannabis use. Its symptoms include
rather than symptoms of anxiety and early life psychosocial an inability to control use, persistent use despite harmful
factors [43, 47]. Frequent cannabis use was associated with consequences, tolerance to the effects of cannabis, with-
bipolar disorder and greater bipolar symptom severity, such drawal symptoms, and craving [21]. Worldwide, 22 million
as mania, rapid cycling, and mixed episodes [47]. There is people are estimated to meet criteria for CUD, similar in
strong early evidence that recent cannabis use is associated number to opioid use disorders (27 million people) [56].
with negative long-term symptomatic and treatment out- It is estimated that 22% of people who ever use cannabis
comes across anxiety or mood disorders [46]. The litera- meet criteria for CUD, increasing to 33% in those who use
ture is heterogeneous and associations may not be causal. weekly or daily [57]. Key risk factors include being male,
Heavier and more frequent cannabis use was associated with of younger age [57] and using high-potency cannabis [58].
suicidal ideation and suicide attempts in adolescents and Increases in cannabis potency have been associated with a
young adults [48, 49]. The increases in suicide observed may faster progression to first onset of symptoms [59]. Psycho-
reflect more impulsive behaviours. The causal pathways and social treatments such as motivational enhancement therapy,
mechanisms underlying the association between cannabis cognitive behavioral therapy, and contingency management
use, cannabis use disorder and anxiety or mood disorders produce greater reductions in cannabis use than control
remain unclear [40]. treatments [60]. There are no approved pharmacotherapies
for the treatment of CUD [61].
Psychotic disorders
Pregnancy
Meta-analyses of case–control and cohort studies report
a robust association between cannabis use and the risk There is consistent evidence that regular cannabis use dur-
of a psychotic disorder, and a dose–response relationship ing pregnancy increases the risk of maternal anemia and
European Archives of Psychiatry and Clinical Neuroscience (2025) 275:281–292 285

neonatal problems such as reduced birth weight and the need “days before preceding the events” [72]. Potential confound-
for intensive care treatment [62]. Emerging preliminary evi- ing effects of co-substance use (e.g., tobacco and alcohol) in
dence suggests that prenatal cannabis exposure may have studies need to be acknowledged. The endogenous cannabi-
subtle yet enduring effects on memory and achievement in noid system may also provide an array of potential benefits,
children and adolescents [63]. There is limited evidence that particularly in the role of CBD as a neuroprotector for stroke
some problems may persist into adulthood, such as delin- [73]. Rigorous studies supporting these positive effects are
quency, substance use and abuse, memory deficits, and psy- missing [72].
chotic symptoms [64].
Hyperemesis syndrome
Respiratory system
Cannabis can cause recurring bouts of nausea, vomiting and
There is consistent evidence of an association between acute
intense abdominal pain amidst other acute gastrointestinal
cannabis smoking and bronchodilation and between regu-
symptoms that are severe enough to prompt users to seek
lar cannabis smoking and respiratory symptoms of cough,
medical help [23]. These cyclical episodes occur with pro-
wheezing, and phlegm [65]. It is unclear the extent to which
longed, high-dose cannabis use and are alleviated by hot
these effects are due to cannabis alone or its combined used
baths and showers and abstinence from cannabis [74]. The
with tobacco or other confounders. THC vaping has been
mechanism are not well understood but the disruption of the
associated with pulmonary injury due to the contaminants in
endocannabinoid system is a possible contributing factor.
electronic cigarettes and vaping pens (e-cigarette, or vaping,
product use associated lung injury or EVALI) [66].
Brain alterations
Cancer
Case–control neuroimaging studies of the brain with high-
Three case–control studies investigated the association resolution provide early evidence for altered brain integrity
between cannabis use and development of testicular germ in brain regions with a high density of CB1 receptors in
cell tumors [67]. The strongest association was found for heavy cannabis users [75]. Specifically, chronic cannabis
non-seminoma development and weekly cannabis use. The users have smaller volumes of the orbitofrontal cortex, a
evidence is inconclusive for testicular seminomas, and lung brain region implicated in motivation, and the hippocam-
cancer, neck and head cancers because of the possible roles pus, a brain area implicated in stress, learning and memory
of tobacco use, and other confounders. [32]. Cannabis users and people intoxicated with THC had
altered function in the same regions and in brain striatal
Cardiovascular risks areas implicated in reward processing. These alterations
were more consistently observed in persons with a history
Effects of cannabinoids on cardiovascular parameters seem of chronic cannabis use [76].
to be complex and differential. They affect vasculature and
myocardium directly via specific receptors and exert indirect
Mortality
effects through the central and peripheral nervous system.
THC acutely stimulates the cardiovascular system, increases
Risk of death due to cannabis toxicity is very low, but there
heart rate and produces a change in blood pressure. This
is a link between cannabis use at high doses and lethal motor
occurs primarily due to sympathetic nervous system activa-
vehicle collisions, cardiac pathophysiology and possibly sui-
tion and parasympathetic nervous system inhibition [68].
cide [17, 77, 78]. It is unclear whether mortality is related to
There are case reports of adverse cardiovascular risks in
cannabis use, predisposing factors or combinations thereof.
chronic cannabis users (e.g., myocardial infarctions, tachy-
cardia, dysrhythmias, hypotension, and orthostatic hypoten-
sion) [68–70]. There is consistent evidence of a temporal
association between the onset of cardiovascular events and Efficacy and safety of cannabis‑based
both chronic and acute cannabis intoxication [71]. There medicines
is emerging evidence that cannabis use is associated with
an increased risk of acute coronary syndrome, especially Due to their pharmacological properties, cannabis or can-
in those with a history of cardiovascular events. There is nabinoids are used for medical purposes (Table 1) [79, 80].
a strong temporal link between cannabis exposure and the The literature on therapeutic effects of cannabis is limited
occurrence of stroke (i.e., ischemic), including chronic use to studies of delta-9-tetrahydrocannabinol (THC) and can-
and acute intoxication with onset ranging from “24 h” to nabidiol (CBD).
286 European Archives of Psychiatry and Clinical Neuroscience (2025) 275:281–292

Table 1  Cannabis or cannabinoids used for medical purposes [79, 80]

Source Commercial name Indication

Synthetic delta-9-tetrahydrocannabinol (THC)a Marinol, Syndros (dronabinol) Anorexia with weight loss in AIDS wasting syn-
drome
Synthetic cannabinoid similar to delta-9-tetrahy- Cesamet and Canemese (nabilone) Anorexia with weight loss in AIDS wasting syn-
drocannabinol (THC) drome
Nausea and vomiting associated with chemotherapy,
usually after previous treatments have failed
Plant based delta-9-tetrahydrocannabinol (THC) & Sativex (nabiximols) Muscle spasticity resulting from multiple sclerosis
cannabidiol (CBD)a
Plant derived cannabidiol (CBD)a Epidiolex Seizures associated with Lennox-Gastaut syndrome
or Dravet syndrome in patients 1 years of age and
older
Seizures associated with tuberous sclerosis complex
in patients 1 year of age or older
Cannabis preparations Raw cannabis, magistral prepara- No approved indication
tions, standardized cannabis
preparations
a
Approved by FDA in the USA

Chronic pain small beneficial effects on muscle spasticity, primarily in

patients with multiple sclerosis and possibly in those with
Chronic pain includes neuropathic pain, fibromyalgia, rheu- spinal cord injuries and motor neuron disease. Benefits
matoid arthritis and any pain in one or more anatomical were more evident on patient than on physician ratings
region that persists or recurs for longer than 3 months and is of muscle spasticity [91, 92]. Cannabinoids may increase
associated with significant emotional distress or functional slightly treatment discontinuation due to adverse events,
disability [20]. There is limited and inconsistent evidence nervous system and psychiatric disorders [93]. Nabiximols
that cannabinoids reduce chronic non-cancer pain by at least are only recommended if other treatments are ineffective,
30% but not more than 50% [81]. Cannabinoids may alle- and a 4-week trial produces at least a 20% reduction in
viate neuropathic pain in some patients [82], but there is spasticity-related symptoms [88].
insufficient evidence for other types of chronic pain [83, 84].
There is weak evidence for patient-perceived benefits [85].
Studies of the efficacy of cannabinoids for chronic pain treat- Chemotherapeutically induced nausea
ment have usually been short-term (<12 weeks, partly only a and vomiting (CINV)
few days) [86]. Cannabinoids have been administered as an
oromucosal spray and combined with approved analgesics CINV is one of the few indications for which cannabi-
(e.g., opioids, anticonvulsants, or antidepressants) [82]. Mild noids (dronabinol, nabilone, levonantradol, nabiximols)
to moderate central nervous or gastro-intestinal side effects are approved by regulatory agencies such as the FDA in
are more common with cannabinoids than with placebo but the USA. As an adjuvant treatment, they showed higher
severe side effects are rare [13]. Cannabinoids are recom- antiemetic effects than placebo or conventional anti-
mended as second or third-line medications for chronic pain emetics [94]. These findings suggest that cannabinoids
[87]. A large number of patients need to be treated to achieve as promising therapeutic option for complicated CINV
a clinical benefit [81] and they are costly for patients [88]. conditions (e.g., break-through, anticipatory or refrac-
There is also evidence that tolerance to the analgesic effects tory). It should be pointed out here that newer antiemetics
of cannabinoids develops with repeated use, which might superseded many of the older antiemetics that cannabi-
limit their long-term benefits [89]. Medical cannabinoids noids were compared against. Only one RCT has compared
may improve sleep in people living with chronic pain, but cannabinoids to a guideline medication (ondansetron) for
the magnitude of benefit is small [90]. CINV prevention [95] and none compared them to new
generation drugs (5-HT3- or NK1 antagonists or neuro-
Muscle spasticity leptics) [94].
In cancer anorexia cachexia syndrome patients’ cannabi-
Some cannabinoids (nabiximols, dronabinol, oral and noid treatment did not significantly improve appetite, oral
oromucosal THC and THC/CBD, medicinal hemp) have intake, or anorexia-related quality of life [96].
European Archives of Psychiatry and Clinical Neuroscience (2025) 275:281–292 287

Epilepsy diseases such as rheumatoid arthritis and inflammatory

bowel disease [103].
CBD has recently been approved as Antiseizure medica-
tions for children and adults. A meta-analysis [97] shows Safety
that CBD is moderately efficacious both as standalone and
adjunct therapy with clobazam for controlling refractory Medical uses of THC-based cannabinoids are associated
epilepsy in patients with Dravet syndrome, Lennox-Gastaut with an increased risk of short-term adverse effects, but
syndrome, and tuberous sclerosis complex. severe side effects are rare [13]. THC-based products may
alter thinking and perception, produce dizziness, lighthead-
Eye disease edness and sedation particularly in older adults [104]. CBD
is not intoxicating and has fewer safety concerns than THC,
Effects of CBD-based cannabinoids are heterogeneous. but there is the potential for liver toxicity, drug-drug interac-
THC-based effects on intraocular pressure are short-timed tions, and there is poor regulatory oversight of CBD prod-
and reduced by the development of tolerance. Safe and effec- ucts [105]. THC and/or CBD increase SSRI concentrations
tive drugs are already available on the market [98]. in adolescents, and coadministration of CBD and SSRIs
increases the risk of cough, diarrhea, dizziness, and fatigue
[106]. A systematic review recently estimated the preva-
Mental disorders lence of cannabis use disorders in people who use medici-
nal cannabis is estimated at 25% (CI: 18–33%) [107]. This
To date, only very few studies tested the effects of medici- risk could be higher in people with chronic non-cancer pain,
nal cannabinoids to improve symptoms of mental disorders, mental health or substance use disorders [107]. An overview
e.g. opioid dependence, cannabis use disorder, schizophre- of adverse events reported in medicinal cannabis studies,
nia and schizophrenic psychoses, depressive disorders, post- medicinal cannabis product information, and post-marketing
traumatic stress disorder, anorexia nervosa, Tourette’s syn- adverse event data can be found elsewhere [108].
drome, attention-deficit hyperactivity disorder [99], autism
spectrum disorder [100, 101] or dementia [13, 15]. In these
studies, THC and/or CBD were administered with other Conclusions
pharmacotherapies and/or psychotherapy [15]. The paucity
of data does not allow any guidance on the therapeutic use of Cannabis is often used recreationally for its intoxicat-
cannabinoids for treating mental disorders within a regula- ing effects and may have acute adverse health effects and
tory framework [102]. impair the ability to safely drive a vehicle. More intense
and prolonged patterns of use are linked with impaired: (1)
Other medical conditions educational attainment, (2) physical health (e.g., brain alter-
ations, respiratory and cardiovascular risks, fetal damage,
The evidence for therapeutic benefit of cannabis-based medi- hyperemesis syndrome), (3) mental health (e.g., motivation,
cine is weak or conflicting for other medical conditions (see CUD, psychosis, mood and anxiety disorders), (4) suicide
eText Box 2). Due to the role of the ECS in modulating and mortality.
inflammation, there is considerable interest in the therapeu- The increasing potency of cannabis products over the last
tic potential of cannabinoids in the treatment of autoimmune few decades may increase the risk of addiction, impaired

eText Box 2  Efficacy of cannabis-based medicines: other medical conditions

Multiple sclerosis: Tremor and nocturia was not consistently improved by cannabinoids (nabiximols, oral cannabinoids) [109]
Parkinson’s disease: In 3 out of 4 studies cannabinoids did not improve symptoms or those of l-dopa-induced dyskinesia (CBD, THC/CBD,
nabilon, SR141716) [110]
Huntington’s chorea: Three small trials (84 participants) tested cannabinoids (CBD, nabilon, nabiximols) [102]. Significant treatment effects
were found for nabilone
Dystonia: Two trials (24 participants) indicated lack of evidence on the use of cannabinoid for dystonia [102, 110]
Dementia: There is uncertain evidence for the efficacy and tolerability of cannabinoids in dementia [111, 112]
Gastrointestinal disorders: No firm conclusions could be drawn on the benefits and side effects of cannabinoids in adults with active Crohn’s
disease (3 small RCTs, n = 93 participants) [113] or ulcerative colitis (2 RCTs, n = 92 participants) [114]. In patients with irritable bowel
syndrome, cannabis and cannabinoids did not produce clinical remission or reduce inflammation (15 nonrandomized studies, 5 RCTs) but
patient-reported symptoms and quality of life were significantly improved [115]
288 European Archives of Psychiatry and Clinical Neuroscience (2025) 275:281–292

cognitive performance and mental disorders. It also appears benefits of medical and nonmedical cannabis use should be
to have increased the prevalence of overdosing, requiring a high policy priority. In locations where the recreational
emergency medical care. Though, the literature is sparse the purchase of cannabis is legal, the general public and espe-
evidence suggests that increased potency (higher THC con- cially vulnerable individuals (e.g., pregnant or breastfeed-
centrations) increases the acute and chronic adverse effects ing women, people with health problems) should also be
of cannabis. informed about the risks of self-medication. Clinicians
Confounding of cannabis use by tobacco and other drug administering cannabinoids need to be mindful of patients’
use complicates the interpretation of evidence on the harm- cardiovascular risks and vulnerability to stroke. Doctors
ful long-term health effects of cannabis smoking. There is should take into account the risk of cannabis use disorder
debate about the extent to which the association between and other adverse effects when prescribing cannabis or can-
cannabis use and health risks is causal. Case–control and nabinoids for mental or physical health problems.
cohort studies are subject to unmeasured confounding—a
Supplementary Information The online version contains supplemen-
limitation which may be overcome using genetically sensi- tary material available at https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 00406-0​ 24-0​ 1880-2.
tive designs. More rigorous data is needed on health out-
comes associated with increased cannabis potency, diversity Author contributions All authors contributed to the manuscript. Mate-
of cannabis products and new routes of administrations. rial preparation, literature research and analysis were performed by
Eva Hoch, Chris Friemel, Valentina Lorenzetti and Tom Freeman. The
Evidence on the therapeutic benefits of cannabis is draft of the manuscript was written by Eva Hoch, Wayne Hall, Chris
limited to a few conditions and cannabinoids have been Friemel, Valentina Lorenzetti, Tom Freeman and Nora Volkow. All
approved as therapeutics for a handful of indications. Strong- authors read and approved the final manuscript.
est evidence for therapeutic benefit has been shown for CBD
Funding Open Access funding enabled and organized by Projekt
as an adjunctive treatment for intractable epilepsy in children DEAL.
and adults. THC may have benefits in improving spastic-
ity, chronic pain, and chemotherapy-induced nausea and Declarations
vomiting. The evidence base is inconclusive or too small
to give treatment recommendations for neuropsychiatric Conflict of interest The authors have no conflict of interest.
disorders and other medical conditions. A major challenge
Open Access This article is licensed under a Creative Commons Attri-
in clinical trials is the absence of “standard” cannabinoids. bution 4.0 International License, which permits use, sharing, adapta-
The multiple preparations tested (e.g., dronabinol, Sativex tion, distribution and reproduction in any medium or format, as long
spray, smoked cannabis flower) include different cannabi- as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
noids (e.g., THC, THC/CBD, CBD). Varied modes of use were made. The images or other third party material in this article are
complicate standardized dosage and comparability in intra- included in the article’s Creative Commons licence, unless indicated
and interindividual effects. Cannabinoids are also commonly otherwise in a credit line to the material. If material is not included in
used in addition to standard medications. This makes it diffi- the article’s Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will
cult to estimate the effects of “pure” cannabinoids and drug- need to obtain permission directly from the copyright holder. To view a
drug interactions, as seen for THC and/or CBD and SSRIs in copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
adolescent patients. Cannabinoids are commonly well toler-
ated. In comparison with placebo, they have more adverse
effects, which are transient and not severe in most cases. The
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