Neuroprotection or Neurotoxicity of Illicit Drugs on Parkinson’s Disease

Abstract

Parkinson’s Disease (PD) is currently the most rapid growing neurodegenerative disease and over the past generation, its global burden has more than doubled. The onset of PD can arise due to environmental, sporadic or genetic factors. Nevertheless, most PD cases have an unknown etiology. Chemicals, such as the anthropogenic pollutant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amphetamine-type stimulants, have been associated with the onset of PD. Conversely, cannabinoids have been associated with the treatment of the symptoms’. PD and medical cannabis is currently under the spotlight, and research to find its benefits on PD is on-going worldwide. However, the described clinical applications and safety of pharmacotherapy with cannabis products are yet to be fully supported by scientific evidence. Furthermore, the novel psychoactive substances are currently a popular alternative to classical drugs of abuse, representing an unknown health hazard for young adults who may develop PD later in their lifetime. This review addresses the neurotoxic and neuroprotective impact of illicit substance consumption in PD, presenting clinical evidence and molecular and cellular mechanisms of this association. This research area is utterly important for contemporary society since illicit drugs’ legalization is under discussion which may have consequences both for the onset of PD and for the treatment of its symptoms.

Alpha-Synuclein Aggregation Pathway in Parkinson’s Disease: Current Status and Novel Therapeutic Approaches

“…This can be explained by the higher levels of melanin and neuromelanin in the substantia nigra , which may have a neuroprotective effect, but also by socioeconomic state and industrialization level. Environmental risk factors, especially early-life exposure to persistent organic pollutants (POPs), namely organochlorine pesticides, that increase PD prevalence [ 34 , 38 , 39 , 40 ]. The link between pesticide toxicity (e.g., dieldrin) and cellular pathology processes in PD (α-Syn aggregation, damage, and death of dopaminergic neurons) has been confirmed [ 39 , 41 , 42 ].…”

“…However, the opposite results and a weak connection between air pollution and PD development were also reported [ 50 ]. In addition, the increased PD incidences might be associated with the consumption of illicit drugs, such as amphetamine-like stimulants and heroin [ 40 ].…”

“…Cigarette smoking, consumption of coffee and beverages containing high levels of antioxidants, such as black and green tea, non-steroidal anti-inflammatory (e.g., ibuprofen) drug uptake, physical activity, and a diet based on fruits, vegetables, and fish have a protective action against PD [ 36 ]. Phytocannabinoids, which interact with the endocannabinoid system, may play a neuroprotective role in PD [ 40 ].…”

Novel Psychoactive Substances: The Razor’s Edge between Therapeutical Potential and Psychoactive Recreational Misuse

“…The hallmark of these pathologies is the accumulation of misfolded and aggregated proteins associated with neuroinflammation, infection, mitochondrial dysfunction and excitotoxicity. Phytocannabinoids and synthetic cannabinoids appear to be neuroprotective either by binding to the CB1 or CB2 receptors [ 127 ] and are used worldwide by patients with neurodegenerative diseases. Therefore, cannabinoid receptor agonists are a research field for therapeutic purposes.…”

What Do We Know About Medical Cannabis in Neurological Disorders and What Are the Next Steps?

“…In a preclinical study investigating the role of a CB2 receptor agonist on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a mouse model of PD managed in 2017, the use of a CB2 agonist reversed the depletion of CB2 and thus increased the levels of dopamine and improved the behavior of PD mice ( Shi et al, 2017 ). Cannabinoids seem to be protective by binding to the CB1 receptor, inhibiting the dopamine beta hydroxylase activity and decreasing glutamate levels or by binding to CB2, reducing neuroinflammation ( Ferreira et al, 2020 ). All these considerations suggest therapeutic benefits of cannabis in PD.…”