Parkinson Parkinson’s disease is a degenerative disorder, which affects the central nervous system by causing the destruction of the dopamine-producing cells in an area of the brain known as the substantia nigra. The motor functions are first to be affected; as it progresses, cognitive decline, dementia and depression can take hold.
Dyskinesia is a common symptom of Parkinson’s disease (PD). The term refers to involuntary movements of the muscles; symptoms may manifest as uncontrolled twitching or shaking, progressing to extremely slow (or even total lack of) movement. In PD patients treated for prolonged periods with Levodopa (a naturally-occurring precursor to dopamine, which increases dopamine levels in the brain), a specific form known as Levodopa-induced dyskinesia can occur. This form can cause chorea (“dancing” movements of the feet and hands), dystonia (sustained muscular contractions leading to twisted, abnormal posture) and athetosis (slow, writhing movements).
The cannabinoid receptors of the central nervous system are densely clustered in an area of the substantia nigra known as the pars reticula, an area that is fundamentally involved with dopamine signaling to the striatum of the basal ganglia, the region primarily responsible for the regulation of motor activity. Cannabinoid receptors are also present in high numbers in the basal ganglia themselves. Thus, the natural transmission of endocannabinoids is thought to play a role in these fundamental and related processes.
Various studies have indicated that agonization of the cannabinoid receptors by administration of exogenous cannabinoids may assist in the reduction of Levodopa-induced dyskinesia and other motor difficulties in PD patients. A 2002 study on non-human primates concluded that this was indeed the case, as did a 2007 study on rats that utilized the synthetic agonist WIN 55,212-2. However, studies on humans have proved inconclusive thus far. A small clinical trial of seventeen individuals conducted in the UK in 2004 concluded that there was no objective or subjective improvement, while a 2014 observational study of twenty-two patients indicated improvements in tremor (shaking), rigidity and bradykinesia (slow movements).
Abnormal apoptosis of dopamine-producing neurons in the pars compacta (the other main subdivision of the substantia nigra) is thought to be the primary mechanism of Parkinson’s disease. It is not known precisely how this phenomenon occurs, but it has been repeatedly demonstrated that treatment with dopamine receptor agonists can have beneficial effects, as they make up for the loss of neurons by stimulating the remaining ones to produce extra dopamine.
The endocannabinoid system is known to be heavily involved with the regulation of the natural processes of apoptosis—a form of controlled cell death that is a fundamental part of normal metabolic function. In some cases, cannabinoids have been shown to induce apoptosis (for example, in several forms of cancer), but there is also evidence that they can exert a protective effect and reduce excessive rates of apoptosis in certain diseases.
It is postulated that PD may occur due to presence of a compound known as oxidopamine, which differs slightly in structure from dopamine in that it also contains a hydroxyl group (-OH). Its structural similarity allows it to be transmitted to the pars compacta via the dopamine reuptake transporters, whereupon it systematically destroys the dopaminergic (dopamine-producing) neurons.
A study published in 2005 demonstrated that injection of oxidopamine into the brains of mice led to a sharp reduction in dopamine levels, and that administration of delta-9-THC, CBD and the non-selective synthetic cannabinoid HU-210 exerted a permanent neuroprotective effect. The fact that CBD had this effect indicates that the mechanism is dependent on the CB2-receptors (as CBD has negligible affinity for the CB1-receptor), which mediate the anti-inflammatory effects of the compounds and preserve cells from excessive apoptosis.
Sufferers of PD often have sleep-related issues, which can negatively affect the immune system and reduce patients’ capacity to fight off its progression. The disease usually affects older individuals, who often experience insomnia even if they do not suffer from PD itself. Indeed, the insomnia experienced by PD sufferers often differs from typical age-related insomnia; Parkinson’s patients usually have little difficulty in falling asleep, but have severe difficulty remaining asleep throughout the night, and in falling back to sleep if awoken. Some patients report increased incidence of nightmares and excessively vivid dreams, and some also report excessive daytime sleepiness.
Cannabis is well-known to induce sleep, and has been used to do since ancient times in various cultures.
Furthermore, one of the primary symptoms of cannabis withdrawal in dependent users is insomnia. It is thought that both delta-9-THC and CBD have a role to play in the regulation of sleep—specifically, CBD is thought to induce sleep, while delta-9-THC is believed to cause residual sedation (i.e. feelings of sleepiness subsequent to awaking). While this effect of THC may be disadvantageous for those suffering from excessive daytime sleepiness, it may assist in enabling patients with disrupted night-time sleep to fall asleep again.
If you follow the latest advances in dietary supplements for health and wellbeing you may already have heard of CBD products, even if you’ve never seen a cannabis plant. There is increasing and compelling evidence that adding CBD to your diet can potentially alleviate and protect against a variety of conditions.
Up to 40% of individuals afflicted by PD exhibit symptoms of depression, which can negatively affect disease progression in various ways. It is thought that there is a genetic component to the likelihood of PD-afflicted individuals suffering depression, and that polymorphisms of the CNR1 gene—which encodes for the expression of the CB1-receptors—may have a fundamental role to play.
A study published in Nature in 2005 indicated that individuals with a particular polymorphism consisting of two long-chain alleles in the CNR1 gene were less likely to develop depression as a symptom of PD. It was also noted that depression was more likely in patients with akinetic PD (rigidity and loss of movement) than in those with tremoric or mixed-type PD. Furthermore, various studies have indicated that depression is often accompanied by changes in levels of endogenous levels of cannabinoids such as anandamide and 2-AG in the prefrontal cortex, an area heavily involved in mood regulation and decision-making.
While more research must be done to ascertain the precise relationship between PD, CNR1 expression and depression, there is definite therapeutic potential in manipulation of the endocannabinoid system to reduce symptoms of depression in PD-afflicted individuals.