. Author manuscript; available in PMC: 2015 Jun 18.

Published in final edited form as: Nat Rev Neurosci. 2015 Jan;16(1):30–42. doi: 10.1038/nrn3876

Table 1.

Possible endocannabinoid-system-based approaches for the treatment of neurodegenerative disorders.

eCB-system-based drugs	Rationale	Advantages	Disadvantages	Disease	Refs^*
Inhibitors of eCB cellular reuptake and enzymatic hydrolysis (by FAAH, MAGL, ABHD6)	Mimic the beneficial neuromodulatory effects of CB1 activation and the anti-inflammatory effects of CB2 activation in a time-and tissue-selective manner	Activity-dependent control of therapeutic effect, and fewer side effects	Indirect activation of non-CB1, non-CB2 receptors (with FAAH inhibitors) Possible receptor desensitization at high dose (MAGL inhibitors)	Multiple sclerosis Alzheimer’s disease (depending on model and disease phase) Parkinson’s disease	116, 1136, 147, 150
Inhibitors of MAGL	Inhibition of 2-AG-derived inflammatory prostaglandins	Activity-dependent control of therapeutic effect, fewer side effects	Inhibition of beneficial effects of prostaglandins in other tissues or organs	Alzheimer’s disease Parkinson’s disease	126–128
CB2 agonists	Reduction of inflammatory component of disease	Relative lack of psychotropic effects compared to CB1 agonists	Possible receptor desensitization at high dose May favour leukocyte infiltration due to chemotaxis	Huntington’s disease Amyotrophic lateral sclerosis Multiple sclerosis	145, 151–153
CB1 antagonists or inverse agonists	Reduction of the neurochemical imbalance due to prolonged alterations of eCB signalling	Already tested in humans	Potential psychiatric adverse events (anxiety, depression)	Parkinson’s disease and Alzheimer’s disease (depending on model and disease phase)	141, 142, 154

2-AG, 2-arachidonoyl-glycerol; ABHD6, α,β hydrolase 6; CB1, cannabinoid receptor 1; eCB, endocannabinoid; FAAH, fatty acid amide hydrolase 1; MAGL, monoacylglycerol lipase.

Selected references.