There are marked differences in the knowledge on the medical uses of cannabis and cannabinoids in different diseases. For nausea and vomiting associated with cancer chemotherapy, anorexia and cachexia in HIV/AIDS, spasticity in multiple sclerosis and spinal cord injury there is strong evidence for medical benefits. For many other indications, such as epilepsy, movement disorders and depression there is much less available data.
Clinical studies with single cannabinoids or, less often with whole plant preparations (smoked marijuana, encapsulated cannabis extract) have often been inspired by positive anecdotal experiences of patients employing crude cannabis products. The anti-emetic, the appetite enhancing, relaxing effects, analgesia, and therapeutic use in Tourette's syndrome were all discovered in this manner.
Incidental observations have also revealed therapeutically useful effects in a study with patients with Alzheimer's disease wherein the primary issue was an examination of the appetite- stimulating effects of THC. Not only appetite and body weight increased, but disturbed behaviour among the patients also decreased. The discovery of decreased intraocular pressure with THC administration in the beginning of the 1970s was also serendipitous. For this reason, more surveys have been conducted in the past decade questioning individuals that use cannabis therapeutically.
(L. Volicer and colleagues):
A placebo-controlled crossover design, with each treatment period lasting 6 weeks, was used to investigate effects of dronabinol in 15 patients with a diagnosis of probable Alzheimer's disease who were refusing food. (...) Body weight of study subjects increased more during the dronabinol treatment than during the placebo periods. Dronabinol treatment decreased severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first. Adverse reactions observed more commonly during the dronabinol treatment than during placebo periods included euphoria, somnolence and tiredness, but did not require discontinuation of therapy. These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer's disease.
Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Int J Geriatr Psychiatry 1997;12(9):913-919.
So far, there is only one clinical study that examined the effect of cannabinoids in Alzheimer's disease, the study by Dr. Volicer and colleagues of the E. N. Rogers Memorial Veterans Hospital, Bedford (USA) with THC (dronabinol).
Localization of central cannabinoid receptor in the brain as well as results obtained from animal studies suggest that cannabinoids might be effective in the treatment of neurological movement disorders. So far, clinical trials in a limited number of patients provide evidence that cannabinoids are useful in the treatment of tics in Tourette-Syndrome and other hyperkinetic movement disorders such as dystonia.
To date only anecdotal reports are available investigating the clinical effect of cannabinoids in the treatment of Parkinson's disease. In a 1990 study no change in clinical symptomatology occured in 5 patients suffering from Parkinson's disease when smoking a marihuana cigarette. In another study the effect of cannabidiol (CBD) has been investigated in 8 patients suffering from dystonia, a hyperkinetic movement disorder. While there was a beneficial effect of CBD on dystonia, a deterioration of "coexisting parkinsonian features" was noted in 2 of these patients.
However, several animal studies provide evidence that in Parkinson's disease there is not only a reduction of dopamine concentrations but that there might also be an abnormalitiy in the central cannabinoid receptor system. Furthermore, it has been suggested that dopamine and endocannabinoids may have a close functional relationship. In an animal model of Parkinson's disease a sevenfold increase of the levels of endocannabinoids was found. Treatment with anti-parkinsonian drugs (dopamine receptor agonists) resulted in an improvement of parkinsonian symptoms. Simultaneously, the increased levels of endocannabinoids were reduced.
In addition, it has been suggested from animal studies that treatment with L-Dopa (an anti-parkinsonian drug) resulted in changes of the central CB1 receptor system (increased numbers of cannabinoid receptors in specific brain regions). In animal models of Parkinson's disease it has been demonstrated that treatment with anti-parkinsonian drugs improved voluntary movements while co-administration of cannabinoids produced Parkinson-like symptoms.
Based on available investigations it can be speculated that cannabinoid receptor blocking drugs (antagonists) - acting exactly the opposite compared to cannabinoids - might be useful in the treatment of Parkinson's disease. However, so far the effect of cannabinoid receptor antagonists has not been investigated in patients with Parkinson's disease.
(Sieradzan and colleagues):
Levodopa (L-Dopa) is the most effective anti-parkinsonian drug known so far. However, long term treatment with L-Dopa is often complicated by the incidence of levodopa-induced dyskinesia. Therapeutic options for managing these hyperkinetic movements are limited. We performed a randomised, double-blind, placebo-controlled, crossover trial in 7 patients with Parkinson's disease to investigate the effect of the cannabinoid receptor agonist nabilone in the treatment of levodopa-induced dyskinesia. Our results demonstrated a significant reduction of dyskinetic movements after treatment with nabilone. Nabilone had no effect on the antiparkinsonian action of L-Dopa. Surprisingly, from animal studies it has been demonstrated that a potent cannabinoid receptor antagonist (SR141716A) as well has antidyskinetic actions. We suggest that nabilone might act preferentially in another brain region than SR141716A. Both actions, however, may result in a reduction of dyskinetic movements.
Modified according to: Sieradzan KA, Fox SH, Hill M, Dick JPR, Crossman AR, Brotchie JM. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson's disease: a pilot study. Neurology 2001;57:2108-2111.