Cannabinoids: a new frontier for the treatment of Parkinson´s disease

The first evidences about the use of cannabis arise from the second millennium BC, when Assyrians used cannabis or, as they called it, “the drug that takes away the mind” for its psychoactive, mind-altering effects and for its medical properties. Since it was brought to the western world in the 18^th century, its use has been a source of controversy. Surprisingly, research on cannabis has advanced slowly. The major reason was the lack of knowledge about its basic chemistry. Unlike morphine and cocaine, which were isolated and used for research since the 19^th century,  the chemical structures of the psychoactive constituents of cannabis were not isolated until the 1960s. There are over 400 chemicals in cannabis, 80 of them unique to this plant. The exact chemical composition differs between plant species, the parts of the plant and growing conditions. Once the chemistry of the plant was elucidated and the psychoactive molecules identified, it was possible to find the bases of the endocannabinoid system, which is particularly relevant to functions associated with the central nervous system such as pain, mood or apetite. The elements of the endocannabinoid system are highly expressed in brain structures related to movement control, suggesting that they could also be involved in movement disorders such as Parkinson’s disease.

Parkinson´s disease is a chronic neurodegenerative disorder that affects 1% of people over age 60. The disease was first described in 1817 by Dr. James Parkinson and it results from loss of cells in various parts of the brain. The exact cause of Parkinson´s disease is unknown, although it is accepted that a combination of genetic and environmental factors are necessary to develop this disorder. The main brain region affected in patients is called substantia nigra and contains neurons that release the neurotransmitter dopamine. These neurons are lost in Parkinson´s disease, making it difficult for patients to control or direct their movements. The main symptoms are slowness of movement, rigidity, resting tremor and postural instability. The presence of non-motor symptoms is also common and very often has a major impact in the patient’s quality of life. Among others, these symptoms include cognitive impairment, mood disorders or sleeping problems. 

Currently, there is no cure for Parkinson´s disease but medication to increase the brain´s supply of dopamine is used to treat the motor symptoms. At the beginning of the treatment, patients experience a significant improvement. Unfortunately, the benefits of the drugs diminish over time, some side effects appear (such as involuntary movements called dyskinesias), and the non-motor symptoms become more evident.

Nowadays, the main challenge in biomedical research in Parkinson´s disease is the development of new therapeutic strategies to slow down, stop or even reverse the neurodegenerative process. Motor signs appear when about 30% of dopamine neurons are lost. Since degeneration of dopamine neurons results in a profound alteration of the endocannabinoid system in the brain, an interesting question is to determine whether the cannabinoid system constitutes a new therapeutic target for Parkinson´s disease. 

Our group has recently reported that specific modulation of elements of the cannabinoid system has a remarkable neuroprotective activity in parkinsonian animals. An advantage of these compounds is that they exert their function without showing any psychotropic effect.  Together with other evidences, we can conclude from our studies that the cannabinoid system is a promising therapeutic target for Parkinson´s disease and other neurodegenerative diseases such as infantile epilepsy, or spasticity. More research and clinical trials are needed to tease out the therapeutic use of cannabinoids. 

Marisol Aymerich

Biochemistry and Genetics