HUNTINGTON'S DISEASE & Cannabis studies
Science & Research
1981 - Study ~ Tetrahydrocannabinol potentiates reserpine-induced hypokinesia.
1986 - Study - EFFECTS OF CANNABIDIOL IN HUNTINGTON'S DISEASE.
1999 - Study ~ Cannabis in movement disorders.
2003 - Study ~ The endocannabinoid system and Huntington's disease.
2005 - Study ~ Cannabinoid control of motor function at the basal ganglia.
2006 - Study ~ UCM707, an inhibitor of the anandamide uptake, behaves as a symptom control agent in models of Huntington's disease and multiple sclerosis, but fails to delay/arrest the progression of different motor-related disorders.
2006 - Letter - Nabilone Could Treat Chorea and Irritability in Huntington's Disease.
2007 - Study ~ Cannabinoids and neuroprotection in motor-related disorders.
2008 - Study ~ Altered Lipid Metabolism in Brain Injury and Disorders.
2008 - Study ~ The endocannabinoid system in Huntington's disease.
2008 - Study ~ Role of CB2 receptors in neuroprotective effects of cannabinoids.
2009 - Study ~ Cannabinoids and neurodegenerative diseases.
2009 - News ~ Medical Marijuana and Huntington's Disease.
2011 - Study ~ Prospects for cannabinoid therapies in basal ganglia disorders.
2012 - Study ~ Cannabinoid modulation of neuroinflammatory disorders
Huntington's disease patients.
EFFECTS OF CANNABIDIOL IN HUNTINGTON'S DISEASE
Neurology 36 (Suppl 1) April 1986 p. 342
Reuven Sandyk, Paul Consroe, Lawrence Z. Stern, and Stuart R. Snider, Tucson, AZ
Cannabidiol (CBD) is a major nonpsychoactive cannabinoid of marijuana. Based on reports indicating possible efficacy of CBD in dystonic movements (Neurology 1984; 34 [Suppl 1]: 147 and 1985; 35 [Suppl 1]: 201), we tried CBD in three patients with Huntington's disease (HD).
The patients;, aged 30 to 56, had HD of 7 to 12 years' duration. Their condition has been slowly progressive and unresponsive to prior therapy with neuroleptics. Orally administered CBD was initiated at 300 mg/d and increased 1 week later to 600 mg/d for the next 3 weeks. Mild improvement ( 5 to 15%) in the choreic movements was documented using the tongueprotrusion test (Neurology [Minneap} 1972; 22: 929-33) and a chorea severity evaluation scale (Br J Clin Pharmacol 1981; 11: 129-51) after the first week.
Further improvement (20 to 40%) was noticed after the second week of CBD, and this remained stable for the following 2 weeks.
Except for transient, mild hypotension, no side effects were recorded, and laboratory tests were normal. Withdrawal of CBD after 48 hours resulted in return of choreic movements to the pre-CBD state.
(Supported in part by NINCDS grant #NS15441)
Nabilone Could Treat Chorea and Irritability in Huntington’s Disease
J Neuropsychiatry Clin Neurosci 18:553-554, November 2006
© 2006 American Neuropsychiatric Association
SIR: Huntington’s disease causes chorea and psychiatric abnormalities. Psychiatric symptoms were found in one study in 51 out of 52 patients. Dysphoria, agitation, irritability, apathy, and anxiety were found in above 50% of the patients sampled.
Many sources postulate that cannabinoids could have a beneficial effect on the symptoms of Huntington’s disease, especially on choreatic movements. As well as providing possible symptomatic relief in Huntington’s disease, there is also some evidence that cannabinoids might have a neuroprotective effect which could delay the onset of symptoms by delaying or preventing the death of striatal neurons. This neuroprotective effect has also been postulated by other sources.
To date there are only two reports on the use of cannabinoids in Huntington’s disease in the literature. Cannabidiol, a nonpsychotropic cannabinoid, had no effect on chorea severity in 15 patients. In one single patient, single dose, uncontrolled open clinical trial using nabilone, 1.5mg, the chorea increased significantly. We present a case of a female patient with irritability, which improved after the introduction of cannabis. This improvement was maintained by treatment with nabilone.
The patient was a 43-year-old female who died in December 2003. She developed symptoms of Huntington’s disease at the age of 24 and her husband gave up paid employment to care for her in 1990 when she was 30 years old. In 1995, he reported difficulties in caring for his wife. These difficulties were related to personality changes due to her illness.
She increasingly resisted help from professionals, especially care assistants, and refused any suggestion of short-term respite care. She became disinhibited and frequently undressed herself and walked around naked inside and occasionally outside the house. She exhibited a number of dangerous behaviors, such as leaving taps running and fires burning, and leaving burning cigarettes around. Her husband became concerned about the effect that the care for his chronically ill wife was having on his son, who was born in 1984.
The patient went into residential care in 1996. The patient’s husband visited two or three times every week and he always took his wife out for a trip. These trips were difficult because of the patient’s refusal to be strapped into the car or her wheelchair, which sometimes resulted in falls caused by violent choreic movements when he was unable to physically hold her in the chair because he was using his hands for some other purpose.
In 2001, he began to give his wife cannabis to smoke when he took her out on these regular trips. When he returned his wife to the nursing home after these visits the staff were aware of a significant difference in the patient. The cannabis appeared to improve her mood and she was calmer and more relaxed.
Prior to the introduction of cannabis she was extremely impatient and would get angry if required to wait even a few minutes for a cigarette. After taking cannabis, she was able to wait a while without screaming and throwing things. The patient also willingly accepted the use of a car seat belt and wheelchair harness.
In December 2001, the local general practitioner prescribed a regimen of nabilone, a synthetic 9-keto cannabinoid, which the patient began taking, 1mg each day. The husband and the nursing home staff both reported improvements in behavior and reduction of chorea coinciding with the introduction of cannabis and maintained by daily taking nabilone.
This report has many limitations. It is a single case report and no measurements were taken at the time of the introduction of cannabis and nabilone. The information was obtained by interviewing the husband and staff from the care home in 2005.
The symptoms of Huntington’s disease do change over time and the movements are different in the later stages of the disease. However both the husband and the staff are sure that the introduction of cannabis was beneficial and greatly improved the patient’s quality of life in her last years. There is need for further trials to establish the therapeutic use of cannabinoids in the symptomatic treatment of Huntington’s disease.
The first author receives an unrestricted educational grant from Cambridge Laboratories, which holds the European marketing rights for nabilone.
- Paulsen JS, Ready RE, Hamilton JM, et al: Neuropsychiatric aspects of Huntington’s disease. J Neurol Neurosurg Psychiatry 2001; 71:310–314
[Abstract/Free Full Text]
- Consroe P: Brain cannabinoid systems as targets for the therapy of neurological disorders. Neurobiol Dis 1998; 5:534–551
- Craufurd D, Thompson JC, Snowden JS: Behavioral changes in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol 2001; 14:219–226
- Goutopoulos A, Makriyannis A: From cannabis to cannabinergics: new therapeutic opportunities. Pharmacol Therapeutics 2002; 95:103–117
- Aiken CT, Tobin AJ, Schweitzer ES: A cell-based screen for drugs to treat Huntington’s disease. Neurobiol Dis 2004; 16:546–555
- Baker D, Pryce G: The therapeutic potential of cannabis in multiple sclerosis. Expert Opin Investig Drugs 2003; 12:561–567
- Croxford JL, Miller SD: Towards cannabis and cannabinoid treatment of multiple sclerosis. Drugs Today 2004; 40:663–676
- Russo E: Future of cannabis and cannabinoids in therapeutics. J Cannabis Therapeutics 2003; 3:163–174
- Consroe P, Laguna J, Allender J, et al: Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav 1991; 40:701–708
- Muller-Vahl KR, Schneider U, Emrich HMl: Nabilone increases choreatic movements in Huntington’s disease. Mov Disord 1999; 14:1038–1040[CrossRef][Medline]
The endocannabinoid system as a target for the treatment of motor dysfunction
Br J Pharmacol. 2009 Apr;156(7):1029-40. Epub 2009 Feb 13
Departamento de Bioquímica y Biología Molecular and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Facultad de Medicina, Universidad Complutense, Madrid, Spain.
There is evidence that cannabinoid-based medicines that are selective for different targets in the cannabinoid signalling system (e.g. receptors, inactivation mechanism, enzymes) might be beneficial in basal ganglia disorders, namely Parkinson's disease (PD) and Huntington's disease (HD).
These benefits not only include the alleviation of specific motor symptoms [e.g. choreic movements with cannabinoid receptor type 1 (CB(1))/transient receptor potential vanilloid type 1 agonists in HD; bradykinesia with CB(1) antagonists and tremor with CB(1) agonists in PD], but also the delay of disease progression due to the neuroprotective properties demonstrated for cannabinoids (e.g. CB(1) agonists reduce excitotoxicity; CB(2) agonists limit the toxicity of reactive microglia; and antioxidant cannabinoids attenuate oxidative damage).
In addition, extensive biochemical, anatomical, physiological and pharmacological studies have demonstrated that:
(i) the different elements of the cannabinoid system are abundant in basal ganglia structures and they are affected by these disorders;
(ii) the cannabinoid system plays a prominent role in basal ganglia function by modulating the neurotransmitters that operate in the basal ganglia circuits, both in healthy and pathological conditions; and (iii) the activation and/or inhibition of the cannabinoid system is associated with important motor responses that are maintained and even enhanced in conditions of malfunctioning and/or degeneration.
In this article we will review the available data regarding the relationship between the cannabinoid system and basal ganglia activity, both in healthy and pathological conditions and will also try to identify future lines of research expected to increase current knowledge about the potential therapeutic benefits of targeting this system in PD, HD and other basal ganglia disorders.
- [PubMed - indexed for MEDLINE]
- PMCID: PMC2697699