Epidyolex 100 mg/ml oral solution: Summary of Product Characteristics
- Population
- Patients with Lennox-Gastaut syndrome, Dravet syndrome or tuberous sclerosis complex
- Product
- Epidyolex (a different cannabidiol medicine)
- Design
- Regulatory product information
- Finding
- Licensed CBD medicine for certain severe epilepsies. Side effects include sleepiness and raised liver enzymes (especially with valproate); interacts with clobazam.
- Limitations
- Epilepsy populations at higher doses per kg; not evidence about psychosis.
Source: Epidyolex 100 mg/ml oral solution: Summary of Product Characteristics. Electronic Medicines Compendium. Official source
Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome
- Population
- 120 children and young adults with Dravet syndrome
- Product
- Purified oral CBD solution (not NWPT-SM32300)
- Design
- Randomised, double-blind, placebo-controlled trial
- Finding
- CBD 20 mg/kg/day reduced convulsive seizures versus placebo. Common side effects included diarrhoea, vomiting, fatigue, fever, sleepiness and abnormal liver tests.
- Limitations
- Epilepsy, not psychosis; cited here for safety information.
Source: Devinsky O, et al.. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376(21). DOI 10.1056/NEJMoa1611618 · PubMed 28538134
The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study
- Population
- 901 people with first-episode psychosis and 1,237 controls, 11 sites
- Product
- Street cannabis (THC), not CBD
- Design
- Case-control study
- Finding
- Daily cannabis use, and especially daily use of high-potency (high-THC) cannabis, was associated with higher odds of psychotic disorder.
- Limitations
- Association, not proof of cause; about THC-rich cannabis, not CBD.
Source: Di Forti M, et al.. The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study. Lancet Psychiatry. 2019;6(5):427-. DOI 10.1016/S2215-0366(19)30048-3 · PubMed 30902669
CBD research
Emerging evidence
Opposite effects of Δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology
- Population
- 15 healthy men (plus 6 in a pretreatment experiment)
- Product
- Oral THC and CBD (not NWPT-SM32300)
- Design
- Experimental brain-imaging study
- Finding
- THC and CBD had opposite effects on activity in several brain regions; CBD pretreatment prevented THC-induced psychotic symptoms in a small group.
- Limitations
- Very small, healthy volunteers, single doses; mechanism, not clinical benefit.
Source: Bhattacharyya S, Morrison PD, Fusar-Poli P, et al.. Opposite effects of Δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. 2010;35:764-774. DOI 10.1038/npp.2009.184
CBD research
Emerging evidence
Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial
- Population
- 88 adults with schizophrenia already taking antipsychotics
- Product
- Oral CBD solution, 1,000 mg/day (not NWPT-SM32300)
- Design
- Randomised, double-blind, placebo-controlled; 6 weeks
- Finding
- Positive psychotic symptoms fell more with CBD than placebo (small difference), and clinicians more often rated patients as improved. Generally well tolerated.
- Limitations
- Small, short, add-on treatment in established schizophrenia; not people at clinical high risk.
Source: McGuire P, Robson P, Cubala WJ, et al.. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am J Psychiatry. 2018;175(3):225-231. DOI 10.1176/appi.ajp.2017.17030325 · PubMed 29241357
CBD research
Emerging evidence
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
- Population
- 42 inpatients with acute schizophrenia
- Product
- Oral CBD up to 800 mg/day (not NWPT-SM32300)
- Design
- Randomised, double-blind, active comparator (amisulpride); 4 weeks
- Finding
- Symptoms improved similarly with CBD and amisulpride; CBD had fewer movement side effects, less weight gain and a smaller prolactin rise.
- Limitations
- Small and short; no placebo group, so the size of any CBD effect alone is uncertain.
Source: Leweke FM, et al.. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2:e94. DOI 10.1038/tp.2012.15 · PubMed 22832859
CBD research
Emerging evidenceNegative finding
The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia: a randomized placebo controlled trial
- Population
- 36 outpatients with chronic schizophrenia
- Product
- Oral CBD 600 mg/day (not NWPT-SM32300)
- Design
- Randomised, double-blind, placebo-controlled; 6 weeks
- Finding
- No improvement in cognition or symptoms compared with placebo.
- Limitations
- Small; lower dose than some other studies; stable chronic patients.
Source: Boggs DL, Surti T, et al.. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia: a randomized placebo controlled trial. Psychopharmacology (Berl). 2018;235(7):1923-1932. DOI 10.1007/s00213-018-4885-9 · PubMed 29619533
CBD research
Emerging evidence
Effect of cannabidiol on medial temporal, midbrain, and striatal dysfunction in people at clinical high risk of psychosis: a randomized clinical trial
- Population
- 33 people at clinical high risk (16 CBD, 17 placebo) and 19 healthy volunteers
- Product
- Single oral CBD 600 mg dose (not NWPT-SM32300)
- Design
- Randomised, double-blind, placebo-controlled brain-imaging study
- Finding
- During a memory task, brain activity with CBD was intermediate between the placebo group and healthy volunteers in several regions.
- Limitations
- Single dose; brain-activity measures, not symptoms or outcomes.
Source: Bhattacharyya S, et al.. Effect of cannabidiol on medial temporal, midbrain, and striatal dysfunction in people at clinical high risk of psychosis: a randomized clinical trial. JAMA Psychiatry. 2018;75(11):1107-1117. DOI 10.1001/jamapsychiatry.2018.2309
CBD research
Emerging evidenceMixed findings
Effects of short-term cannabidiol treatment on response to social stress in subjects at clinical high risk of developing psychosis
- Population
- 32 people at clinical high risk and 26 healthy volunteers
- Product
- Oral CBD 600 mg/day for 7 days (not NWPT-SM32300)
- Design
- Randomised, double-blind, placebo-controlled experimental study
- Finding
- Anxiety and stress responses to a public-speaking test were intermediate between placebo and healthy volunteers. The cortisol response did not differ significantly from placebo.
- Limitations
- One week; laboratory stress test, not clinical outcomes.
Source: Appiah-Kusi E, et al.. Effects of short-term cannabidiol treatment on response to social stress in subjects at clinical high risk of developing psychosis. Psychopharmacology (Berl). 2020. PubMed 31915861
CBD research
Emerging evidence
Effects of cannabidiol on symptoms in people at clinical high risk for psychosis
- Population
- 33 people at clinical high risk (16 CBD, 17 placebo)
- Product
- Oral CBD 600 mg/day for 21 days (not NWPT-SM32300)
- Design
- Randomised, placebo-controlled; published as a short research letter
- Finding
- After adjusting for starting scores, symptom and distress scores were lower with CBD than placebo; CBD was well tolerated.
- Limitations
- Very small, three weeks, short-letter format; not yet confirmed in a larger trial.
Source: Bhattacharyya S, Appiah-Kusi E, Wilson R, et al.. Effects of cannabidiol on symptoms in people at clinical high risk for psychosis. World Psychiatry. 2024;23(3):451-452. DOI 10.1002/wps.21253 · PubMed 39279373
Critical aspects affecting cannabidiol oral bioavailability and metabolic elimination, and related clinical implications
- Population
- Review of human pharmacokinetic studies
- Product
- Cannabidiol in general (not NWPT-SM32300)
- Design
- Review
- Finding
- Taken by mouth while fasting, only about 6% of a CBD dose is estimated to reach the bloodstream; a high-fat meal increases this about fourfold. Much of each dose is broken down by the liver before reaching the circulation.
- Limitations
- Review of other CBD preparations; figures vary between studies.
Source: Perucca E, Bialer M.. Critical aspects affecting cannabidiol oral bioavailability and metabolic elimination, and related clinical implications. CNS Drugs. 2020;34:795-800. DOI 10.1007/s40263-020-00741-5
A Phase I, randomized, double-blind, placebo-controlled, single ascending dose, multiple dose, and multiple dose food effect trial of the safety and tolerability of highly purified cannabidiol in healthy subjects
- Population
- Healthy adult volunteers
- Product
- Purified CBD oral solution (not NWPT-SM32300)
- Design
- Phase 1 randomised, placebo-controlled trial
- Finding
- Described the safety and tolerability of single and repeated doses of purified CBD in healthy adults, and found that a high-fat meal increased CBD exposure.
- Limitations
- Healthy volunteers; a different CBD product. A published correction exists.
Source: Taylor L, et al.. A Phase I, randomized, double-blind, placebo-controlled, single ascending dose, multiple dose, and multiple dose food effect trial of the safety and tolerability of highly purified cannabidiol in healthy subjects. CNS Drugs. 2018;32:1053-1067. DOI 10.1007/s40263-018-0578-5 · PubMed 30374683
