Cannabis for dyskinesia in Parkinson disease: A randomized double-blind crossover study
Joseph WMcSherry, University of Vermont College of Medicine
Published November 18, 2004
I read Carroll et al's article with interest. Although the outcome was negative,
an unusual finding may warrant further studies and the outcome highlights the
need to consider routes of administration.
The improvement in MMSE in the pilot study could have been followed
with a comparison of MMSE results after the various segments of the
crossover trial, compensating for practice effects. Effects on cognition
are very important as cannabis has been recommended for behavior in
Alzheimer patients. [1]
It is disappointing that patients report benefits from cannabis and
the study found none. If cholera or anorexia is being treated [2],
delivering the drug to the bowel makes sense. Patients using Marinol for
nausea report variability in dose effect from toxicity in 45 minutes to
nothing in two hours, presumably depending on other foods in the bowel and
hepatic enzyme activity.
The authors found peak blood levels of "0.25
ng/mL to 5.4 ng/mL, with no clear dose response." Future studies of
systemic effects should use routes of administration that do not make a
first pass through the liver.
The effects of the mix of metabolites from the first pass
differs from the effects of sublingual or vaporized cannabis is further
illustrated by the observation that patients did not feel better on
cannabis "(treatment effect -0.7, CI -1.5 to 0.2)" in contrast to the
subjective response of some patients and other users. It is possible that only some patients respond favorably and perhaps only to certain
cultivars.
The study does illustrate the complexities of finding the basis of
patients' observation of improvement and oral Cannador does not have a
therapeutic role in the treatment of dyskinesia in this study group.
References
1. 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 Sep;12:913-9
2. Izzo AA, Capasso F, Costagliola A, et al. An endogenous cannabinoid tone attenuates cholera
toxin-induced fluid accumulation in mice Gastroenterology. 2003 Sep;125:765-74
I read Carroll et al's article with interest. Although the outcome was negative, an unusual finding may warrant further studies and the outcome highlights the need to consider routes of administration.
The improvement in MMSE in the pilot study could have been followed with a comparison of MMSE results after the various segments of the crossover trial, compensating for practice effects. Effects on cognition are very important as cannabis has been recommended for behavior in Alzheimer patients. [1]
It is disappointing that patients report benefits from cannabis and the study found none. If cholera or anorexia is being treated [2], delivering the drug to the bowel makes sense. Patients using Marinol for nausea report variability in dose effect from toxicity in 45 minutes to nothing in two hours, presumably depending on other foods in the bowel and hepatic enzyme activity.
The authors found peak blood levels of "0.25 ng/mL to 5.4 ng/mL, with no clear dose response." Future studies of systemic effects should use routes of administration that do not make a first pass through the liver.
The effects of the mix of metabolites from the first pass differs from the effects of sublingual or vaporized cannabis is further illustrated by the observation that patients did not feel better on cannabis "(treatment effect -0.7, CI -1.5 to 0.2)" in contrast to the subjective response of some patients and other users. It is possible that only some patients respond favorably and perhaps only to certain cultivars.
The study does illustrate the complexities of finding the basis of patients' observation of improvement and oral Cannador does not have a therapeutic role in the treatment of dyskinesia in this study group.
References
1. 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 Sep;12:913-9
2. Izzo AA, Capasso F, Costagliola A, et al. An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice Gastroenterology. 2003 Sep;125:765-74