Cannabis

Cannabis is recorded in the Shennong Bencao Jing (Pen-ts’ao Ching), compiled in the first century CE from oral traditions attributed to the emperor Shen Nong. It was used for rheumatic pain, constipation, disorders of the female reproductive system and malaria ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

The Chinese used mainly the seeds as medicine. The surgeon Hua Tuo (2nd century CE) gave a cannabis preparation in wine to anaesthetise patients for operations ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

Medical and religious use of cannabis in India probably began around 1000 BCE, and the Atharva Veda names it among five sacred plants ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

It was used for pain (neuralgia, headache, toothache), for convulsions, as a sleep aid and tranquilliser, as an anaesthetic, for rheumatism and other inflammation, for colic and diarrhoea, as a digestive and appetite stimulant, and for coughs and asthma ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

Three preparations were made, in rising strength: bhang from the dried leaves, ganja from the female flowers, and charas from the resin ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

From India the medical use of cannabis spread to the Middle East. Avicenna included it in his medical writings around 1000 CE ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

Islamic texts describe it as a diuretic, a digestive and a remedy for flatulence and ear pain. In 1464, Ibn al-Badri recorded treating the epileptic son of the caliph’s chamberlain with cannabis resin ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

Cannabis has been known in Africa since at least the fifteenth century, probably brought by Arab traders ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

It was used for snakebite, to ease childbirth, and for malaria, fever, blood poisoning, anthrax, asthma and dysentery ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

Cannabis entered Western medicine through William O’Shaughnessy, an Irish physician in British India. His 1839 work on Indian hemp reported its use for rheumatism, convulsions, and the muscle spasms of tetanus and rabies ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

Cannabis extracts and tinctures were widely used by the end of the nineteenth century. A 1924 medical encyclopedia grouped its uses as a sedative for insomnia and other conditions, and as a painkiller for headache, migraine, neuralgia, period pain and uterine complaints ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

Its use declined in the early twentieth century, partly because plant batches varied so much in strength, and cannabis was removed from the United States Pharmacopeia in 1941 ^{30Reference 30Zuardi · 2006ReviewHistory of cannabis as a medicine: a review — review (history)View study →}.

The cannabinoids differ widely in where they act. Some act on the CB1 receptor, some on CB2, and some on neither. The main ones, in rough order of abundance:

• THC (tetrahydrocannabinol) — the main psychoactive cannabinoid, acting at both CB1 and CB2 receptors. It is linked to the plant’s effects on appetite, nausea and pain, and is mildly stimulating at low doses and sedating at higher ones. Δ⁹-THC is the abundant form, and Δ⁸-THC occurs in small amounts.
• CBD (cannabidiol) — usually the other dominant cannabinoid, and not intoxicating. It acts mostly away from the CB1 receptor: at serotonin 5-HT1A receptors and TRPV1 channels, as an inhibitor of FAAH (the enzyme that breaks down anandamide), and at PPARγ. It has been studied for anti-inflammatory, anti-anxiety, anticonvulsant and mildly sedative effects.
• CBG (cannabigerol) — the non-psychoactive precursor from which many other cannabinoids are made, so plants harvested early are richer in it. It acts at α2-adrenoceptors and at CB1 and CB2, and has anti-inflammatory activity.
• CBC (cannabichromene) — non-psychoactive, acting mainly on TRP ion channels, strongly at TRPA1 and also at TRPV3 and TRPV4. In surveyed drug-type material CBC is below 0.5%, less than CBG and CBN ^{28Reference 28ElSohly et al. · 2024ObservationalA 10-year trend in cannabis potency (2013–2022) in different geographical regions of the United States of America — observationalView study →}. Laboratory work points to anti-inflammatory and mild antidepressant effects, with little human data.
• CBN (cannabinol) — formed as THC oxidises in air, so older or ground material holds more of it. It is at most mildly psychoactive and a weak CB1 agonist. It is marketed as a sleep aid, a reputation that rests largely on early work with aged resin and on CBN given together with THC; its sedative effect alone appears small.
• THCV (tetrahydrocannabivarin) — a close relative of THC with a shorter side chain and much weaker psychoactivity. It suppresses appetite, the opposite of THC.

The remaining cannabinoids — CBDV, CBGV, CBCV, CBL, CBE, CBGM, CBT and CBV — occur in small amounts and have been mapped chemically more than studied for their effects.

Two placebo-controlled trials in Lennox-Gastaut syndrome and one in Dravet syndrome tested pharmaceutical cannabidiol (Epidiolex) added to existing anti-seizure drugs.

In Dravet syndrome, 20 mg/kg/day cut the median monthly number of convulsive seizures from 12.4 to 5.9, against 14.9 to 14.1 on placebo ^{2Reference 2Devinsky et al. · 2017RCTTrial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome — randomised controlled trialView study →}. In Lennox-Gastaut syndrome, drop seizures fell by a median 37–44% on 10–20 mg/kg/day, against 17–22% on placebo ^{3,4Reference 3Devinsky et al. · 2018RCTEffect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome — randomised controlled trialView study →Reference 4Thiele et al. · 2018RCTCannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4) — randomised controlled trialView study →}. A 2025 meta-analysis confirms a dose-related reduction ^{5Reference 5Martimbianco ALC et al. · 2025Meta-analysisCannabis derivatives and their synthetic analogs for treatment-resistant epilepsy — systematic review and meta-analysisView study →}.

These results belong to high-dose purified CBD in these specific epilepsy syndromes, not to consumer CBD oils or smoked cannabis.

Gap: Efficacy is proven only for rare childhood-onset syndromes with prescription-grade CBD; it does not extend to epilepsy in general or to over-the-counter CBD products. Raised liver enzymes occurred in 9% of patients in one trial ^{3Reference 3Devinsky et al. · 2018RCTEffect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome — randomised controlled trialView study →}, and an interaction with clobazam requires monitoring.

Nabiximols is a standardised 1:1 THC:CBD mouth spray, licensed in many countries for multiple sclerosis spasticity that has not responded to first-line drugs. A meta-analysis of three trials in 666 patients found a small reduction in patient-rated spasticity and more responders on nabiximols than on placebo ^{6Reference 6Wade et al. · 2010Meta-analysisMeta-analysis of the efficacy and safety of Sativex (nabiximols) on spasticity in people with multiple sclerosisView study →}, and a 2023 meta-analysis supports it as add-on therapy ^{7Reference 7Kleiner D et al. · 2023Meta-analysisNabiximols is Efficient as Add-On Treatment for Patients with Multiple Sclerosis Spasticity Refractory to Standard Treatment — systematic review and meta-analysisView study →}.

Cochrane rates the evidence low-to-moderate certainty with a small average effect ^{8Reference 8Filippini et al. · 2022Systematic reviewCannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis — Cochrane systematic reviewView study →}. Patient-reported spasticity improves more than examiner-rated measures do.

The effect is modest and partly self-reported, and the standardised spray does not represent smoked or edible cannabis.

Synthetic THC analogues, dronabinol and nabilone, have been licensed anti-sickness drugs since the 1980s. A Cochrane review of 23 trials found cannabinoids more effective than placebo, similar to the older drug prochlorperazine, and preferred by patients over placebo ^{10Reference 10Smith et al. · 2015Systematic reviewCannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy — Cochrane systematic reviewView study →}.

Modern 5-HT3 antagonists are now first-line, and cannabinoids are used for nausea that does not respond to standard drugs, the role the 2024 ASCO guideline endorses ^{26Reference 26Braun et al. · 2024Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline — practice guidelineView study →}.

The trials were run between 1975 and 1991, none compared cannabinoids with modern anti-sickness drugs such as ondansetron, and most were at risk of bias ^{10Reference 10Smith et al. · 2015Systematic reviewCannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy — Cochrane systematic reviewView study →}.

A 2026 Cochrane review of 21 trials in chronic neuropathic pain found no clear effect of THC-dominant, balanced THC:CBD or CBD-dominant medicines on the number of people whose pain halved. Balanced THC:CBD medicines may slightly increase the number reaching 30% relief, but the gain was too small to be clinically relevant. THC-dominant medicines may increase nervous-system side effects ^{9Reference 9Ateş G et al. · 2026Systematic reviewCannabis-based medicines for chronic neuropathic pain in adults — Cochrane systematic reviewView study →}. The 2015 JAMA meta-analysis rated the overall pain evidence moderate-quality ^{1Reference 1Whiting et al. · 2015Meta-analysisCannabinoids for Medical Use: A Systematic Review and Meta-analysisView study →}.

In cancer pain, a 2023 Cochrane review found that nabiximols or THC added to opioids did not reduce pain more than placebo ^{23Reference 23Häuser W et al. · 2023Systematic reviewCannabis-based medicines and medical cannabis for adults with cancer pain — Cochrane systematic reviewView study →}.

Gap: Cancer-pain trials are null ^{23Reference 23Häuser W et al. · 2023Systematic reviewCannabis-based medicines and medical cannabis for adults with cancer pain — Cochrane systematic reviewView study →}, effect sizes elsewhere are small, and side effects such as dizziness and sedation are common.

The anti-anxiety findings belong to cannabidiol rather than the whole plant, and high-THC cannabis can provoke anxiety and paranoia. In a double-blind trial in 24 people with social anxiety, a single 600 mg dose of CBD reduced anxiety during a simulated public-speaking test ^{11Reference 11Bergamaschi et al. · 2011RCTCannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients — randomised controlled trialView study →}, and smaller acute-dosing studies point the same way.

These effects appeared at 300–600 mg CBD, far above the 10–50 mg in most retail products, and no large trial has tested daily CBD for a diagnosed anxiety disorder.

In a phase 2a double-blind trial in people with cannabis use disorder, 400 mg and 800 mg of cannabidiol daily for four weeks reduced cannabis use compared with placebo, while 200 mg was dropped as ineffective ^{12Reference 12Freeman et al. · 2020RCTCannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised trialView study →}.

This is one trial of 82 participants, and it has not yet been replicated.

Many people with Crohn’s disease and ulcerative colitis use cannabis. In an 8-week trial in 56 people with Crohn’s disease, oral CBD-rich cannabis oil improved symptom scores and quality of life, but endoscopy showed no difference from placebo ^{13Reference 13Naftali et al. · 2021RCTOral CBD-rich Cannabis Induces Clinical but Not Endoscopic Response in Patients with Crohn’s Disease — randomised controlled trialView study →}. A 2025 meta-analysis reached the same conclusion ^{14Reference 14Vaid R et al. · 2025Meta-analysisCannabis use in Crohn’s disease: a systematic review and meta-analysis of randomised controlled trialsView study →}.

No trial has shown reduced inflammation or healing of the bowel lining.

THC stimulates appetite through CB1 receptors, and in people with HIV, cannabinoids led to more weight gain than placebo ^{15Reference 15Mücke et al. · 2018Meta-analysisSystematic review and meta-analysis of cannabinoids in palliative medicineView study →}. In people with cancer, the controlled trials found no significant difference from placebo in appetite or calorie intake, and one trial found no advantage over megestrol ^{15,16Reference 15Mücke et al. · 2018Meta-analysisSystematic review and meta-analysis of cannabinoids in palliative medicineView study →Reference 16Razmovski-Naumovski V et al. · 2022Meta-analysisEfficacy of medicinal cannabis for appetite-related symptoms in people with cancer — systematic review and meta-analysisView study →}.

Gap: The cancer-cachexia trials are null, and the supporting HIV-wasting data predate modern HIV therapy.

A 2025 meta-analysis of six trials (1,077 participants) found cannabinoids improved self-reported sleep quality compared with placebo, most clearly in people with insomnia or poor sleep. Products containing THC or other non-CBD cannabinoids had the effect; CBD alone did not ^{18Reference 18da Silva GHS et al. · 2025Meta-analysisEffectiveness of cannabinoids on subjective sleep quality in people with and without insomnia — systematic review and meta-analysisView study →}.

In a crossover trial in 125 people with insomnia, a CBD-terpene formula slightly increased the share of the night spent in deep and REM sleep ^{17Reference 17Wang et al. · 2025RCTEffects of a cannabidiol/terpene formulation on sleep in individuals with insomnia: a double-blind, placebo-controlled, randomized, crossover study — randomised controlled trialView study →}.

The trials are few and short, and regular THC use reduces REM sleep and builds tolerance to its sedation.

Case series and small THC:CBD studies have long reported reduced tics. CANNA-TICS, a trial of nabiximols in 97 adults with chronic tic disorders, found more responders on nabiximols (22%) than on placebo (9%), but did not formally meet its primary endpoint. Secondary analyses suggested benefit in some subgroups ^{19Reference 19Müller-Vahl et al. · 2023RCTCANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders — randomised controlled trialView study →}.

Gap: The largest trial missed its primary endpoint ^{19Reference 19Müller-Vahl et al. · 2023RCTCANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders — randomised controlled trialView study →}, and the rest of the evidence is small studies and open-label experience.

THC lowers the pressure inside the eye for about 3–4 hours, so control would need near-constant dosing and near-constant intoxication, and ophthalmology bodies do not recommend it.

Newer work looks at blood flow instead. In a 2026 crossover trial in 23 people with glaucoma, a single 10 mg dose of dronabinol increased blood flow to the optic nerve for up to 4 hours without changing eye pressure ^{20Reference 20Lindner T et al. · 2026RCTSingle oral administration of dronabinol increases ocular blood flow in patients with glaucoma — randomised controlled trialView study →}.

In cell and animal studies, CBD and THC trigger cancer-cell death across several tumour types ^{22Reference 22Melo ESA et al. · 2025ReviewMechanisms of Cell Death Induced by Cannabidiol Against Tumor Cells: A Review of Preclinical StudiesView study →}. The one human study, a 2006 pilot in nine people with recurrent glioblastoma, infused THC into the tumour. It showed the treatment could be given safely, and median survival was 24 weeks; with no control group, it could not test for a survival benefit ^{21Reference 21Guzmán et al. · 2006Clinical trialA pilot clinical study of delta-9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme — clinical trialView study →}.

Gap: The only human study had nine patients and no control group ^{21Reference 21Guzmán et al. · 2006Clinical trialA pilot clinical study of delta-9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme — clinical trialView study →}. Everything else is laboratory work.

Driving and coordination. THC impairs coordination, reaction time and judgment, and impaired driving is one of its best-established harms. High doses can bring on anxiety, panic or brief paranoia, more often with high-THC, low-CBD material.

Tolerance and dependence. Roughly one in ten users develop some degree of cannabis use disorder, more with early or daily heavy use. Regular breaks keep tolerance down.

Drug interactions. In healthy volunteers, a single dose of CBD-rich cannabis extract (640 mg CBD) raised blood levels of omeprazole, losartan, midazolam and caffeine, showing inhibition of CYP2C19, CYP2C9, CYP3A and CYP1A2 but not CYP2D6, while a THC-only extract had no effect ^{33Reference 33Bansal et al. · 2023Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult ParticipantsView study →}. The same dose raised THC levels too, since THC is cleared mainly by CYP2C9 ^{33Reference 33Bansal et al. · 2023Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult ParticipantsView study →}.

Two weeks of CBD tripled exposure to the transplant drug tacrolimus in healthy volunteers ^{34Reference 34So et al. · 2025A Phase I Trial of the Pharmacokinetic Interaction Between Cannabidiol and TacrolimusView study →}. High-dose CBD can also raise liver enzymes ^{3Reference 3Devinsky et al. · 2018RCTEffect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome — randomised controlled trialView study →}. Cannabis adds to the sedation of alcohol, benzodiazepines and opioids.

Psychosis. In a meta-analysis of ten studies, the heaviest cannabis users had almost four times the risk of psychosis of non-users ^{24Reference 24Marconi et al. · 2016Meta-analysisMeta-analysis of the Association Between the Level of Cannabis Use and Risk of PsychosisView study →}. The THC content of seized US cannabis roughly tripled between 1995 and 2014 while its CBD content halved ^{27Reference 27ElSohly et al. · 2016ObservationalChanges in cannabis potency over the last two decades (1995–2014): analysis of current data in the United States — observationalView study →}. People with a personal or family history of psychosis or schizophrenia should avoid high-THC cannabis.

Heart and lungs. THC raises heart rate and can affect blood pressure, so people with heart disease should be careful. Smoke irritates the airways; vaporised or oral cannabis avoids the cough and bronchitis that come with smoking.

Synthetic cannabinoids. Laboratory-made cannabinoids sold as street drugs, such as “spice”, bind the same receptors far more strongly and unpredictably than plant cannabinoids. They have caused agitation, psychosis, seizures, heart attacks and deaths, and have nothing in common with the plant beyond the receptors they act on.

Legal status varies widely between countries and states, and changes often.

Potential Side-Effects

• Dry mouth and dry/red eyes
• Dizziness or lightheadedness
• Increased appetite
• Fatigue or drowsiness
• Anxiety or paranoia (usually high-THC)
• Rapid heartbeat / palpitations
• Short-term memory and coordination effects
• Nausea (occasionally, especially high doses)
• Cough or bronchitis (smoking only)