CBD in schizophrenia: Current research.

On the occasion of World Schizophrenia Day, we review current research on CBD in this disease. The first thing you should know is that CBD is not currently an approved medication for schizophrenia and its use is not indicated at this time.

The CBD or cannabidiol is a non-psychoactive compound found in cannabis plants. In recent years, this component has been presented as a therapeutic possibility for schizophrenia. However, it is important to note that currently the use of CBD for schizophrenia is still in the research phase, so its use is contraindicated. In this post we review the research on the subject.

What is schizophrenia?

Schizophrenia is a serious mental illness that affects how a person thinks, feels and behaves. Symptoms may include hallucinations, delusions, disorganized speech, erratic behavior and social withdrawal. It is a chronic disease and usually requires long-term treatment.

How is schizophrenia treated?

Treatment may include antipsychotic medications and therapy. Schizophrenia is the most frequent disease within the group of “psychoses”, a term used in psychiatry for diseases in which there is a loss of contact with reality.

What is the relationship between cannabis and schizophrenia?

Schizophrenia has no single cause, but is explained by a combination of genetic and environmental factors. There is a statistical association between some patterns of cannabis use and the subsequent development of schizophrenia (1), which does not imply that cannabis use is a necessary or sufficient cause.

It is also known that, in people diagnosed with schizophrenia, marijuana use increases the symptoms of the disease, the number of hospitalizations and worsens the prognosis.

Is medical cannabis an option for schizophrenia?

Advances in knowledge about cannabinoids have determined that the component of cannabis that exacerbates or worsens schizophrenia is tetrahydrocannabinol (THC). tetrahydrocannabinol (THC) the same compound responsible for the psychotropic and psychoactive effects of marijuana. High doses of THC can produce psychotic symptoms (such as those that appear in schizophrenia) in susceptible persons.

In 1982, it was demonstrated for the first time in humans that cannabidiol (CBD) could reverse these effects produced by THC (2). Therefore, at the present time, research on medical cannabis in relation to schizophrenia is focused exclusively on cannabidiol.

Are there studies suggesting that CBD may be useful in schizophrenia?

CBD has been tested in several of the animal models commonly used to evaluate preclinical antipsychotic drugs. There are studies on genetically engineered mice used in this regard suggesting that CBD administration has antipsychotic properties (3). Also, in animal models, cannabidiol has been shown to enhance brain signaling of anandamide, a process linked to the development of schizophrenia (4). Ultimately, the body of animal research data suggests that CBD may be a good antipsychotic (5).

Are there any human cases in which the effect of cannabidiol on schizophrenia has been proven?

Anecdotal reports of schizophrenic patients who have significantly improved using CBD as part of their medical treatment have been recorded since at least 1995 (6, 7, 8). These cases have been published in prestigious scientific journals accepted by the medical community. But case reporting can never be considered as proof of a drug’s efficacy. It is an indicator used to undertake the next phase: clinical trials.

Clinical trials on the efficacy of CBD in patients with schizophrenia

The results of the only two available quality clinical trials on cannabidiol and schizophrenia were published in 2018. A study on 88 patients in the UK found improvement when CBD was added to the patients’ usual treatment for 6 weeks (9). Another U.S. study with a similar design on 36 patients found no beneficial effect (10).

What doses of CBD have been used in clinical trials on cannabidiol and schizophrenia?

In the human clinical trials to which we have just referred, the dose used by the British team was 1,000 mg of CBD per day orally, and that used by the U.S. team. was 600 mg of cannabidiol daily. It is likely that the difference in results can be explained, at least in part, by the different dosage.

Are there more clinical trials currently underway?

Yes. There are ongoing clinical trials on the use of CBD for schizophrenia, with a large number of patients, in institutions as prestigious as the Mannheim Institute of Mental Health (Germany) (11), the University of Copenhagen (12), the Center for Cannabis Research at the University of California (13) or King’s College London (14).

Most of these clinical trials are recruiting patients or already underway, and results are expected to be available between 2023 and 2024. These studies use doses of 1000 mg per day of CBD, although some of the trials exploring specific aspects use doses of 300 mg – 400 mg per day of CBD.

How does CBD work for schizophrenia?

Commercially available antipsychotics are very effective drugs for some symptoms of schizophrenia, such as delusions and hallucinations. But its main drawback is the adverse effects: sedation, drowsiness, difficulty in concentrating, obesity and diabetes, muscle problems, sexual problems…

Many patients with schizophrenia can lead reasonably normal lives while taking prescribed medication. But side effects are the most frequent cause of medication discontinuation, so having antipsychotics with fewer side effects is a priority. The few adverse effects of CBD make its potential use as an antipsychotic particularly interesting.

CBD and medicines for schizophrenia

Can CBD become a substitute for other antipsychotic drugs?

It is very important to emphasize that in all clinical trials available so far, CBD has been added to conventional medication. That is, they are studies that compare the effect of adding CBD or placebo to the treatment a patient is taking.

The antipsychotic effect of CBD would allow, under medical prescription, to reduce the dose of conventional antipsychotics, reducing the frequency and severity of the adverse effects that, as we have already pointed out, are the main problem of the available drugs.

There are no data to suggest that CBD can be used as an antipsychotic in isolation. In this sense, the substitution of an antipsychotic drug for cannabidiol in a patient with schizophrenia is absolutely contraindicated.

Are there interactions between CBD and antipsychotic drugs?

There are theoretical and laboratory data indicating that CBD could modify the blood concentrations of the two most commonly used antipsychotics: risperidone and olanzapine (15). However, there are no data to indicate that these preliminary data have an impact on humans. In fact, we have pointed out that all the clinical trials carried out add cannabidiol to the usual medication without any reported incidences in this regard.

Are there other lines of research in relation to CBD and psychotic disorders?

We noted earlier that, in general, marijuana use worsens the condition of people diagnosed with schizophrenia. Despite this, some sufferers continue to use cannabis in a compulsive and disordered manner. The concurrence of two disorders (schizophrenia + cannabis use disorder) is known as “dual pathology” and CBD is an interesting treatment option that is already being implemented (16), although its effectiveness has not yet been proven and it is therefore not advisable.

In summary, CBD or cannabidiol is emerging as a possible therapeutic option for schizophrenia, but more research is needed before we can say for sure.

Ultimately, it is absolutely imperative that schizophrenia patients seek advice from their specialist medical professional before using CBD and other cannabis-derived products.

The purpose of this post is informational and its content is not intended to prevent, diagnose or treat any disease or symptom. Its content can complement, but never replace, professional diagnosis or treatment. CBD is not an approved medication for schizophrenia. Cannactiva products are not medicines. Consult your doctor if you have questions about schizophrenia and before using CBD.

Referencias
  1. Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ. 2002 Nov 23;325(7374):1212-3. doi: 10.1136/bmj.325.7374.1212. PMID: 12446537; PMCID: PMC135493.
  2. Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 1982;76(3):245-50. doi: 10.1007/BF00432554. PMID: 6285406.
  3. Long LE, Malone DT, Taylor DA. Cannabidiol reverses MK-801-induced disruption of prepulse inhibition in mice. Neuropsychopharmacology. 2006 Apr;31(4):795-803. doi: 10.1038/sj.npp.1300838. PMID: 16052245.
  4. Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkötter J, Hellmich M, Koethe D. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012 Mar 20;2(3):e94. doi: 10.1038/tp.2012.15. PMID: 22832859; PMCID: PMC3316151.
  5. Davies C, Bhattacharyya S. Cannabidiol as a potential treatment for psychosis. Ther Adv Psychopharmacol. 2019 Nov 8;9:2045125319881916. doi: 10.1177/2045125319881916. PMID: 31741731; PMCID: PMC6843725.
  6. Makiol C, Kluge M. Remission of severe, treatment-resistant schizophrenia following adjunctive cannabidiol. Aust N Z J Psychiatry. 2019 Mar;53(3):262. doi: 10.1177/0004867418815982. Epub 2018 Dec 13. PMID: 30543310.
  7. Zuardi AW, Crippa JA, Hallak JE, Pinto JP, Chagas MH, Rodrigues GG, Dursun SM, Tumas V. Cannabidiol for the treatment of psychosis in Parkinson’s disease. J Psychopharmacol. 2009 Nov;23(8):979-83. doi: 10.1177/0269881108096519. Epub 2008 Sep 18. PMID: 18801821.
  8. Makiol C, Kluge M. Remission of severe, treatment-resistant schizophrenia following adjunctive cannabidiol. Aust N Z J Psychiatry. 2019 Mar;53(3):262. doi: 10.1177/0004867418815982. Epub 2018 Dec 13. PMID: 30543310.
  9. McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, Taylor A, Wright S. Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial. Am J Psychiatry. 2018 Mar 1;175(3):225-231. doi: 10.1176/appi.ajp.2017.17030325. Epub 2017 Dec 15. PMID: 29241357.
  10. Boggs DL, Surti T, Gupta A, Gupta S, Niciu M, Pittman B, Schnakenberg Martin AM, Thurnauer H, Davies A, D’Souza DC, Ranganathan M. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology (Berl). 2018 Jul;235(7):1923-1932. doi: 10.1007/s00213-018-4885-9. Epub 2018 Apr 5. PMID: 29619533.
  11. Enhancing Recovery in Early Schizophrenia. ClinicalTrials.gov Identifier: NCT02926859
  12. Cannabidiol for Treatment of Non-affective Psychosis and Cannabis Use. ClinicalTrials.gov Identifier: NCT04105231
  13. Effects of Cannabidiol (CBD) Versus Placebo as an Adjunct to Treatment in Early Psychosis. ClinicalTrials.gov Identifier: NCT04411225
  14. Does Cannabidiol Attenuate the Acute Effects of ∆9-tetrahydrocannabinol Intoxication in Individuals Diagnosed With Schizophrenia? A Double-blind, Randomised, Placebo-controlled Experimental Study (INTEGRATE). ClinicalTrials.gov Identifier: NCT04605393
  15. Ujváry I, Hanuš L. Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy. Cannabis Cannabinoid Res. 2016 Mar 1;1(1):90-101. doi: 10.1089/can.2015.0012. PMID: 28861484; PMCID: PMC5576600.
  16. Garel N, Greenway K, Joober R. The antipsychotic potential of cannabidiol: clinical implications for patients with psychosis and comorbid cannabis use disorder. J Psychiatry Neurosci. 2021 Jan 18;46(1):E164-E165. doi: 10.1503/jpn.200114. PMID: 33464779; PMCID: PMC7955839.
  17. CBD Cigarettes Instead of Normal Cigarettes as Innovative Treatment for Schizophrenia. ClinicalTrials.gov Identifier: NCT04700930

Dr. Fernando Caudevilla
Family Physician | Expert in Drug Addictions. He works in different assistance, research and training projects related to drugs, including therapeutic cannabis.

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