CBD’s Supportive Role in Parkinson’s And Seizures

The statements mentioned in this content have not been evaluated by the FDA, and are not intended to prevent, diagnosis, or treat any disease. Always work with your personal healthcare provider.

By Chris D. Meletis, N.D.

Movement disorders like Parkinson’s disease and seizure disorders such as epilepsy are similar but distinct neurological conditions. Despite being characterized by abnormal movements, epilepsy is not classified as a motor disorder.1 Movement disorders are associated with altered function in the basal ganglia of the brain.1 Epilepsy is an occurrence of signs and/or symptoms that arise from abnormal excessive or synchronous neuronal activity in the brain leading to seizures with a high risk of recurrence.However, the two types of disorders have some similarities, and movement disorders can resemble seizures while seizures can resemble movement disorders.1 Another similarity is that both types of disorders respond well to cannabidiol (CBD).

The Endocannabinoid System in Parkinson’s Disease

Parkinson’s disease is one of the most common neurodegenerative disorders, occurring in 1% of people over 60 in age.2 Hallmarks of the disease include impaired motor function (hypokinesia, tremors, and muscle rigidity) and non-motor symptoms such as problems sleeping, cognitive decline, anxiety, depression, and psychotic symptoms.The origination of Parkinson’s disease coincides with a loss of midbrain dopaminergic neurons in the substantia nigra pars compacta (SNpc).4  This causes dopamine levels in the striatum to dramatically decline.By the time motor symptoms manifest, approximately 60% of the dopaminergic neurons have been destroyed.4

The standard treatment for Parkinson’s disease is L-DOPA, a dopamine precursor that elevates concentrations of this neurotransmitter in the striatum, leading to improvements in movement symptoms.Unfortunately, over time, L-DOPA’s effects become less dependable, leading to fluctuations in symptom improvement.6 A common side effect of the drug occurring in half of everyone using it is involuntary movements (dyskinesia).7

Endocannabinoids are endogenously produced substances that act on cannabinoid, vanilloid, and peroxisome proliferator-activated receptors. Endocannabinoids such as anandamide and 2-arachidonoylglycerol, their receptors, enzymes, and downstream signaling targets make up the endocannabinoid system. Evidence in the medical literature indicates substances that target this system can play a supportive role in basal ganglia disorders such as Parkinson’s disease.The benefits of targeting the endocannabinoid system include improvement in motor symptoms and neuroprotection.7

The endocannabinoid system’s beneficial role is supported by evidence that indicates key players in this system are abundantly present in basal ganglia structures and are impaired in motor disorders.Endocannabinoids, their synthesizing and degrading enzymes, and their receptors are highly present in the basal ganglia structures (caudate-putamen, globus pallidus, substantia nigra) compared with other brain areas.7 The endocannabinoid system also regulates dopamine, glutamate, and GABA, the neurotransmitters that are active in the basal ganglia.7,8

CBD’s Supportive Role

Emerging evidence indicates CBD may have a role to play in supporting the health of Parkinson’s patients. In a study of 21 Parkinson’s patients without dementia or other psychiatric comorbidities, participants were given a placebo, CBD (75 mg/day), or CBD (300 mg/day).9 CBD 300 mg/day led to an improvement in well-being and quality of life scores compared with the placebo.

In a four-week, open-label pilot study, six Parkinson’s disease patients suffering from psychosis for at least three months received oral CBD starting with 150 mg/day, in addition to their usual medications.10 After using CBD, participants experienced significant improvement in psychotic symptoms evaluated by the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire. There was also a decline in the total scores of the Unified Parkinson’s Disease Rating Scale in the patients using CBD.

Another group of researchers studied four patients with Parkinson’s REM sleep behavior disorder, a condition associated with the loss of muscle atonia that usually occurs during this stage of sleep, increased nightmares, and movement during dreaming.11 Giving CBD to these people resulted in improved REM sleep and “prompt and substantial reduction in the frequency” of REM sleep behavior occurrences.

CBD and Epilepsy

A number of studies indicate CBD may support the health of people with seizures. In a randomized, double-blind, placebo-controlled 14-week study of Dravet syndrome patients, CBD together with anti-epileptic medications resulted in more significant declines in the frequency of convulsive seizures compared with a placebo.12 Two other randomized, controlled trials studied the use of CBD together with anti-epileptic medications in patients with Lennox-Gastaut syndrome.13,14 These studies determined that using CBD for 14 weeks resulted in significantly less drop seizures compared with the placebo.

In another study, children and adults who had treatment-resistant Lennox-Gastaut or Dravet syndrome were given a highly purified form of CBD plus anti-epileptic drugs.15 At baseline, parents and caregivers recorded  the types and number of seizures experienced. The participants began with a dose of 2-10 mg/kg/day and gradually worked up to a maximum dose of 25-50 mg/kg/day.

At 12 weeks, CBD correlated with a 50% decline in median monthly major motor seizures and 44% less total seizures. Through 96 weeks, there were consistent declines in both seizure types. At 12 weeks, the number of major motor seizures declined by half in 53% of the patients given CBD. A 75% decline in major motor seizures occurred in 23% of the participants using CBD. In 6% of the subjects, major motor seizures completely resolved. In 46% of the people using CBD,  total seizures declined by half, while 26% suffered 75% less total seizures, and in 5%, the seizures went away completely.

In one of the earliest studies on CBD and seizures, 16 patients were given 200-300 mg daily of CBD or placebo in a randomized, double-blind manner.16 The participants remained on their antiepileptic medications, but these drugs had not been able to control the patients’ seizures.

In the CBD group, 4 of the 8 subjects remained nearly free of seizures throughout the study. Three other patients had partial improvement after the CBD intervention. One patient did not derive any benefit from CBD. In the placebo group, seven patients remained unchanged and only one patient clearly improved.

Conclusion

Key players in the endocannabinoid system are highly present in the basal ganglia, which is impaired during motor disorders. CBD, which interacts with the endocannabinoid system, may support basal ganglia functioning, leading to a reduction in motor symptoms. Studies also indicate CBD may play a supportive role in reducing seizures. As always it is vitally important to work under the guidance of a skilled healthcare provider with these and other health conditions.  Starting with low dosing and titrating up slowly is the recommended approach many practitioners adhere too.  It should be noted that CBD can slow in some circumstances the clearance of prescription medications and other substances, so working closely with ones pharmacist about potential interactions is important.

References:

  1. Freitas ME, Ruiz-Lopez M, Dalmau J, et al. Seizures and movement disorders: phenomenology, diagnostic challenges and therapeutic approaches. J Neurol Neurosurg Psychiatry. 2019;90(8):920-8.
  2. Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 2017 Aug;124(8):901-5.
  3. Klockgether T. Parkinson’s disease: clinical aspects. Cell Tissue Res. 2004 Oct;318(1):115-20.
  4. Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron. 2003 Sep 11;39(6):889-909.
  5. Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review.JAMA. 2014 Apr 23-30;311(16):1670-83.
  6. Jankovic J. Motor fluctuations and dyskinesias in Parkinson’s disease: clinical manifestations. Mov Disord. 2005;20 Suppl 11:S11-6.
  7. Peres FF, Lima AC, Hallak JEC, et al. Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders?Front Pharmacol. 2018;9:482.
  8. Fernández-Ruiz J, Gonzáles S. Cannabinoid control of motor function at the basal ganglia. Handb Exp Pharmacol. 2005;(168):479-507.
  9. Chagas MH, Zuardi AW, Tumas V, et al. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. J Psychopharmacol. 2014 Nov;28(11):1088-98.
  10. Zuardi AW, Crippa JA, Hallak JE, et al. Cannabidiol for the treatment of psychosis in Parkinson’s disease. J Psychopharmacol. 2009 Nov;23(8):979-83.
  11. Chagas MH, Eckeli AL, Zuardi AW, et al. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson’s disease patients: a case series. J Clin Pharm Ther. 2014 Oct;39(5):564-6.
  12.  Devinsky O, Cross JH, Laux L, et al. Trial of Cannabidiol for Drug-resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25;376(21):2011-20.
  13. Devinsky O, Patel AD, Cross JH, et al. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 May 17;378(20):1888-97.
  14. Thiele EA, Marsh ED, French JA, et al. Cannabidiol in Patients with Seizures Associated with Lennox-Gastaut Syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Mar 17;391(10125):1085-96.
  15. Laux LC, Bebin EM, Checketts D, et al. Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results. Epilepsy Res. 2019 Aug;154:13-20.
  16. Cunha JM, Carlini EA, Pereira AE, et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology. 1980;21(3):175-85.