Cannabis: Currently Approved Indications and Therapeutic Potential


Dr. Paul Morrison

Clinical Senior Lecturer
Institute of Psychiatry
King’s College London

NHS Consultant Psychiatrist
The Maudsley Hospital, London
 
 
Last updated: December 7, 2017
 
This presentation reviews indications for currently approved cannabis products (dronabinol and nabilone). It also discusses the therapeutic potential of CBD in psychiatry (psychosis) and other medical conditions (epilepsy, oncology).

In this section, we’ll discuss approved cannabis formulations in the USA and outside the USA and therapeutic potential in psychiatry and other medical conditions.

 

Approved cannabis formulations

 

The FDA approved the use of two cannabinoid products, dronabinol (Marinol) and nabilone (Cesamet). Dronabinol contains synthetic Δ9-THC and nabilone is a synthetic cannabinoid.

 

FDA-approved indications for dronabinol and nabilone are: anorexia associated with weight loss in patients with AIDS, and nausea and vomiting associated with cancer chemotherapy, usually in patients who have failed to respond to first line antiemetics.

 

Sativex is the commercial name of an oral spray containing a 1:1 ratio of THC and CBD. Sativex has been approved in many EU countries, Canada and in some countries in Latin America.

 

It is indicated for treating spasticity in patients suffering from MS.

 

Recently, in the largest review of the literature to date, the National Academy of Sciences, Engineering and Medicine concluded that there is conclusive or substantial evidence for the use of cannabis in treating chronic pain, nausea and vomiting related to chemotherapy and spasticity related to MS.

 

CBD: therapeutic potential as antipsychotic

 

Although high potency CB1 agonists can be detrimental, the natural cannabis plant in its more balanced form contains molecules which may be therapeutic in a mental health regard.

 

CBD or cannabidiol appears to have antipsychotic properties in its own right. Early results from pioneering researchers in Brazil hinted that CBD could be effective in schizophrenia.

 

Thus, the natural cannabis plant may contain ingredients which are pro-psychotic, THC, and also, antipsychotic in the case of CBD. It may be the balance between the two ingredients which determines the risk for mental health.

 

A German group carried out a head to head clinical trial in patients with schizophrenia, in which CBD was compared against the antipsychotic drug amisulpride.

 

At the end of the four weeks, the group randomized to CBD showed as much improvement as those randomized to receive amisulpride. Although the trial was small, these results were highly encouraging, especially as the side effects of CBD were minimal.

 

Recently, our own group in London has looked at CBD in a larger sample of schizophrenic patients. The trial was slightly longer than the German study at six weeks.

 

Also, patients were under treatment with existing antipsychotic drugs, but their improvement had only been partial, which is often the case in practice.

 

The idea was to test whether adding CBD could lead to further improvements, and this turned out to be the case. Compared to placebo, those who were given CBD showed an improvement in their psychosis and their overall mental health. That study is currently submitted for publication.

 

CBD as anticonvulsant

 

CBD is also an effective anticonvulsant. Indeed, one of the first properties of CBD to be discovered was efficacy in animal models of epilepsy. CBD may translate for epilepsy sooner than for psychotic illness.

 

An early trial in patients in the 1970s showed that CBD was effective for temporal lobe epilepsy.

 

There has been renewed interest in using CBD as an anticonvulsant particularly in treatment-resistant childhood epilepsy and syndromes such as Lennox-Gastaut.

 

Trials have been positive, and it is hoped that CBD emerges as a new treatment for epilepsy. Much of that work is currently ongoing in the USA.

 

Other potential applications

 

Cannabinoids are also showing promise in oncology. A recent small phase two clinical trial for glioma found that the addition of a 1:1 combination of THC-CBD to standard treatment yielded a one-year survival rate of 83% compared to 53% for those who received placebo.

 

Other cannabinoid molecules may have therapeutic applications. The plant contains over 60 natural cannabinoids and may represent a source of new medicines. The molecule THCV for instance may be effective for the metabolic syndrome.

 

Dronabinol and nabilone are FDA-approved for anorexia associated with weight loss and patients with AIDS, and from nausea and vomiting in cancer patients who have not responded to first line treatments.

 

Sativex is approved in many countries outside the USA.

 

Sativex combines THC and CBD and it’s approved for the treatment of spasticity in multiple sclerosis.

 

CBD appears to have antipsychotic properties and is a potent anticonvulsant.

 

References

  1. Marinol (Dronabinol) [Prescribing Information]. North Chicago, IL; AbbVie Inc;
  2. Cesamet (Nabilone) [Prescribing Information]. High Point, NC Unimed Pharmaceuticals, Inc
  3. Sativex Oromucosal Spray (Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)) [Prescribing Information] Cambridge, UK. GW Pharma Ltd
  4. National Academies of Sciences, Engineering, and Medicine. (2017). The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. National Academies Press
  5. Zuardi AW, Morais SL, Guimarães FS, Mechoulam R. Antipsychotic effect of cannabidiol. J Clin Psychiatry. 1995 Oct;56(10):485-6
  6. Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry 2012;2:e94
  7. Cunha JM, Carlini EA, Pereira AE, Ramos OL, Pimentel C, Gagliardi R, Sanvito WL, Lander N, Mechoulam R. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology. 1980;21(3):175-85
  8. O’Connell, B. K., Gloss, D., & Devinsk, O. (2017). Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy & Behavior
  9. https://www.gwpharm.com/about-us/news/gw-pharmaceuticals-achieves-positive-results-phase-2-proof-concept-study-glioma

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