Knowledge Centre
Science and evidence
How cannabis acts on the body, and what the clinical literature establishes about its benefits, indication by indication.
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The Knowledge Centre holds the prescribing pathway, Motagon documents, certificates of analysis and clinical evidence summaries. It is available to doctors, pharmacists, nurses and other healthcare professionals whose professional registration we have verified.
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The endocannabinoid system
Cannabis acts through the endocannabinoid system, a receptor system whose function is to maintain homeostasis. Cannabinoids interact with it through several distinct mechanisms, which is why a single plant can affect conditions as different as pain, nausea, appetite, inflammation, spasticity and post-traumatic stress disorder.
CB1 receptors are concentrated in the central nervous system and influence mood, memory and pain perception. THC binds most strongly to CB1, which accounts for its psychoactive effects. CB2 receptors are most abundant in the immune system, where they influence inflammatory processes. CBD interacts with other receptors, often by mechanisms other than direct activation.
The body produces its own endocannabinoids, principally anandamide and 2-AG, together with the enzymes that degrade them. More than 140 phytocannabinoids have been identified in the plant. The proposal that endocannabinoid deficiency underlies conditions such as fibromyalgia, irritable bowel syndrome and migraine remains a hypothesis rather than an established finding.
What the evidence supports, by indication
A summary of where the published literature is strongest, where it is thin, and where it is negative.
| Indication | Evidence position | Notes |
|---|---|---|
| Chronic neuropathic pain | Most studied, modest benefit | The most studied indication, and the one Czech GPs may prescribe for under R52.1. Cochrane 2018: 30% relief in 39% against 33% on placebo, NNT 11, with more adverse events. The evidence in detail. |
| Spasticity in multiple sclerosis | Established | Supported by controlled trials; the basis for several authorised cannabinoid medicines. |
| Chemotherapy-induced nausea and vomiting | Established | Long-standing evidence, including for synthetic cannabinoids. |
| Appetite and cachexia | Moderate | Demonstrated in cancer and HIV/AIDS populations. |
| Sleep disturbance secondary to pain | Moderate | Consistently reported as a secondary benefit across pain studies. |
| Acute pain | Not supported | No better than placebo for acute or post-operative pain in the 2020 and 2025 meta-analyses; no opioid sparing in randomised trials. |
| Visceral pain | Not supported | Oral THC no better than placebo in chronic abdominal pain in a controlled trial. |
| Cancer pain uncontrolled by opioids | Not supported as add-on | Two phase 3 nabiximols trials missed their primary endpoints and a 2020 meta-analysis of six trials found no reduction in pain from adding cannabinoids to optimised opioids. Symptom benefits (sleep, appetite, nausea) are a separate question. |
This table summarises the position as we read it. It is not a guideline and does not replace national prescribing guidance.
Drug interactions worth checking
THC and CBD are metabolised in the liver by the cytochrome P450 system. In vitro, THC inhibits CYP2C9 most potently, and also CYP1A2, CYP2C19 and CYP3A; CBD inhibits CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A, and the active metabolites of both inhibit several of the same enzymes. At the THC doses typical of inhaled or low-dose oral cannabis, clinically relevant inhibition is unlikely; at the high oral CBD doses used in epilepsy, interactions are documented.
Three interactions deserve attention. Clobazam and its active metabolite rise markedly with concurrent CBD (about 60% and 500% respectively). INR rises have been reported with warfarin in patients taking CBD or THC-containing cannabis, so monitor INR when cannabis is started or stopped. For direct oral anticoagulants (CYP3A4) and clopidogrel (activated via CYP2C19) the interaction is theoretical rather than documented: monitor rather than avoid. Full citations are in the evidence article.
Further reading
- Cannabis in chronic pain: what the evidence supports
- The endocannabinoid system
- Irradiation and terpenes: what the measured data shows
- Chronic pain, patient-level explanation
In preparation: cannabis in oncology, and what changes when a GP takes over the care of a chronic pain patient who has been self-medicating.
Reviewed by [name, role], Motagon s.r.o. Last reviewed 10 September 2026. Intended for healthcare professionals. Not advice on the treatment of an individual patient.