Psychiatric Disorders

The burgeoning prevalence of mental health disorders poses an enormous global challenge. Almost one in two US citizens will receive a DSM-IV diagnosis during their lifetime, and a mood disorder is second only to hypertension in frequency as the presenting condition to British GPs. According to W.H.O., five of the ten leading causes of chronic disability world-wide are psychiatric disorders (major depression, schizophrenia, bipolar disorder, alcohol abuse, obsessive/compulsive neurosis). In the UK, 80 million working days are lost each year as a result of mental illness. There is considerable unmet clinical need as a result of the limited efficacy and potential toxicity of standard medicines.

The therapeutic (and risk) potential of cannabis-based medicines for psychiatric patients remains uncertain for the following reasons: questionable validity of animal models for psychiatric disorders; conflicting results from laboratory studies; questionable reliability and validity of clinical diagnoses; limited availability of controlled human data. Observations deriving from smoked cannabis or recreational users are unreliable for many reasons, including selection bias, inappropriate pharmacokinetics, reliance on self-report, and uncontrollable confounding factors.

On the basis of laboratory evidence, anxiety and depression are promising targets for cannabinoid medicines and there are some preliminary human data in support of thisi. Emerging evidence suggests that the cannabinoid, cannabidiol (CBD), possibly in combination with other cannabinoids, may have potential utility in schizophrenia not only as an anti-psychotic, but also in the alleviation of the metabolic and inflammatory abnormalities associated with the diseaseii. CB1 antagonists may have a role in relapse-prevention in the treatment of addictioniii. Other possible targets for the future based on human anecdote or limited laboratory research include bipolar affective disorder, post-traumatic stress syndrome, eating disorders, and insomnia. For the future, manipulation of the endocannabinoid system through inhibition of FAAHivor the anandamide transportervoffers exciting therapeutic possibilities for many of these conditions.

GW is currently investigating with potential of cannabinoids as treatments for psychiatric disorders in collaboration with Otsuka.

References:

i. Robson P (2005) Human studies of cannabinoids and medicinal cannabis. In Handbook of Experimental Pharmacology – Vol 168 Cannabinoids (ed R Pertwee) pp 738-9. Springer-Verlag Berlin Heidelberg

ii.Robson P, Guy GW, Di Marzo V (2009). Metabolic abnormalities, exaggerated stress response and chronic inflammation in schizophrenia: future therapeutic targets for cannabinoid medicines? Manuscript in preparation

iii.Le Foll B, Goldberg SR (2005). Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence. J Pharmacol & Exp Ther 312, 875-83

iv.Hill MN, Hillard CJ, Bambico FR et al (2009). The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants. Trends in Pharmacol Sci 30, 484-93

v.Mechoulam R, Deutsch DG. (2005). Towards an anandamide transporter. PNAS 102, 17541-2

Fride E, Russo EB. Neuropsychiatry: Schizophrenia, depression, and anxiety. In: Onaivi E, Sugiura T, Di Marzo V, editors. Endocannabinoids: The brain and body's marijuana and beyond. Boca Raton, FL: Taylor & Francis; 2006. p. 371-82.