Legends
Fig. 1. The complexity of the endocannabinoid system. Diagram
showing the components of the
expanded endocannabinoid system
including the biosynthesis and degradation of endocannabinoids in the
CNS. In response to demand, AEA and 2-AG are produced, which can cross
the synaptic cleft and activate presynaptic CB1 receptors resulting in
neurotransmitter inhibition. Biosynthesis and inactivation of AEA
endocannabinoids in postsynaptic neurons is done by FAAH and NAPE-PLD. O
2-AG is hydrolyzed in presynaptic neurons by MAGL, also by enzymes DAGLα
and DAGLβ. Note the complexity of the endocannabinoid system that
interacts with several neuromediators, receptors and new molecular
targets. 2-AcGs; 2-acylglycerols; 2-AG, 2-arachidonoyl-glycerol;
5-HT1A, serotoninergic receptors of the
5-HT1A type; AA, arachidonic acid; Abh4,
alpha-betahydrolase-4; AEA, anandamide; CB1, cannabinoid receptor 1;
CB2, cannabinoid receptor 2; COX-2, cyclooxygenase-2; DAGL,
sn-1-diacylglycerol lipase; ETA, ethanolamide; FAAH, fatty acid amide
hydrolase; GLY, glycerol; GPRs, G protein-coupled receptors; Lyso PLC,
lysoPI-specific PLC; LOX, lipoxygenase; MAGL, monoacylglycerol lipase;
NAES; N-acylethanolamines; NAPE-PLD, N-acyl-phosphatidyl
ethanolamine-specific phospholipase D; PLA1, phospholipase A1; PPARγ,
peroxisome proliferator-actived receptor γ; PTPN22, protein tyrosine
phosphatase nonreceptor type 22; TRPV1, transient receptor potential
vanilloid 1. (Created with BioRender.com).
Fig. 2 . Diagram of interactions and therapeutic effects of CBD
in epilepsy.
2-AG, 2-arachidonoyl-glycerol; 5-HT1A, serotoninergic
receptors of the 5-HT1A type; AEA, anandamide; CB1,
cannabinoid receptor 1; CBD, cannabidiol; GPR55, G protein-coupled
receptor 55; TRPV1, transient receptor potential vanilloid 1. (Created
with BioRender.com).
Fig. 3. Diagram of interactions and therapeutic effects of
THC:CBD in multiple sclerosis. A perivascular and parenchymal infiltrate
of macrophages, B lymphocytes and T lymphocytes is observed in MS, which
cross the blood-brain barrier and destroy the myelin sheath, followed by
partial remyelination by oligodendrocytes (acute inflammatory phase)
than by infiltration of T lymphocytes, oligodendrocyte destruction and
axonal injury will progress to the progressive phase of the disease.
Combined THC:CBD therapy has demonstrated pharmacological activation of
the CB2 receptor strongly associated with suppression of
neuroinflammation and induction of remyelination processes and neuronal
survival. Furthermore, the decrease in astrocyte activity leading to
inhibition of the neuroinflammatory process was also notable. CBD,
cannabidiol; CB1, cannabinoid receptor 1; MS; multiple sclerosis; THC,
Δ9-tetrahidrocanabinol. (Created with BioRender.com).
Fig. 4. Diagram of interactions and therapeutic potential of
phytocannabinoids in Parkinson’s disease. PD is characterized by
dopaminergic damage to the nigrostriatal pathway, dopamine depletion,
excitocicity, accumulation of α-synuclein and Lewy bodies, reduced
trophic support and oxidative stress in the brain region.
Cannabis-derived products have been used for the treatment of PD, such
as: THC and THCV which have shown neuroprotective effects. In the case
of THC, possibly mediated by the CB1 receptor, being also associated
with PPARγ, in the negative regulation of the CB1 receptor and the
restoration of mitochondrial content. THCV is mediated by the CB1
receptor. CBD has been linked to CB2 and TRPV receptors showing
neuroprotective, anti-apoptotic, neuroinflammatory and antioxidant
effects. CB2 receptor-mediated anti-inflammatory and antioxidant effects
have been demonstrated by BCP. 2-AG, 2-arachidonoyl-glycerol; AEA,
anandamide; BCP, β-caryophyllene; CB1, cannabinoid receptor 1; CB2,
cannabinoid receptor 2; CBD, cannabidiol; FAAH, fatty acid amide
hydrolase; NAPE-PLD, N-acyl-phosphatidyl ethanolamine-specific
phospholipase D; PD, Parkinson’s disease; PPARγ, peroxisome
proliferator-actived receptor γ; THC,
Δ9-tetrahidrocanabinol; THCV,
Δ9-tetrahydrocannabivarin; TRPV1, transient receptor potential vanilloid
1. (Created with BioRender.com).