Medical cannabis and its role in Neuroprotection
Medical cannabis has been studied for its potential neuroprotective properties, with promising results indicating it may be a valuable therapeutic tool in the treatment of neurodegenerative diseases.
Cannabis plants contain a variety of active compounds, including over 100 cannabinoids, terpenes, and flavonoids. The two most well-known cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is known for its psychoactive effects, while CBD is non-psychoactive and has been found to have a range of potential therapeutic benefits.
Mechanism of Action
The exact mechanism by which cannabis exerts its neuroprotective effects is not fully understood, but several potential mechanisms have been proposed. One proposed mechanism is through the modulation of the endocannabinoid system. The endocannabinoid system is a complex signaling system in the body that plays a role in a range of physiological processes, including pain sensation, mood, and inflammation. The endocannabinoid system is comprised of two main receptors, CB1 and CB2, which are activated by endocannabinoids and phytocannabinoids. THC has been found to interact with CB1 receptors in the brain, which can lead to a reduction in inflammation and oxidative stress, both of which are associated with neurodegenerative diseases.
Another proposed mechanism is through the modulation of the immune system. Neurodegenerative diseases are associated with chronic inflammation, which can lead to neuronal damage and death. CBD has been found to have anti-inflammatory properties, and can modulate the immune system to reduce inflammation and protect neurons from damage.
Clinical Evidence
A number of preclinical studies have investigated the potential of cannabis-based treatments for the management of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. These studies have found that cannabis-based treatments can be effective in reducing inflammation and oxidative stress, and can protect neurons from damage.
In a study published in the Journal of Alzheimer's Disease in 2014, researchers found that THC was effective in reducing amyloid beta levels, which are associated with the development of Alzheimer's disease. In another study published in the Journal of Neuroimmune Pharmacology in 2015, researchers found that CBD was effective in reducing inflammation and protecting neurons in a mouse model of Parkinson's disease.
In addition to preclinical studies, there have also been a number of clinical trials investigating the potential of cannabis-based treatments for the management of neurodegenerative diseases. While the evidence is still limited, these studies have found that cannabis-based treatments can be well-tolerated and can improve symptoms in some patients.
Side Effects
While cannabis-based treatments for neuroprotection have been found to be generally well-tolerated, they can have side effects in some patients. The most commonly reported side effects of THC include dizziness, dry mouth, and changes in mood or perception. Additionally, THC can interact with some medications, including sedatives and benzodiazepines, which can lead to increased sedation and potential adverse effects. For this reason, it is important for patients to discuss the use of cannabis-based treatments with their healthcare provider. Additionally, patients should be aware of the potential psychoactive effects of THC and should avoid driving or operating heavy machinery while under the influence.
Conclusion
Medical cannabis has shown promising results as a potential neuroprotective agent, with the potential to protect neurons from damage, reduce inflammation, and improve symptoms in patients with neurodegenerative diseases. However, more research is needed to fully understand the mechanisms of action and potential therapeutic benefits of cannabis-based treatments for neuroprotection, and to determine the optimal dosages and formulations for different patient populations. It is important for patients to discuss the use of cannabis-based treatments with their healthcare provider and to be aware of the potential side effects and risks associated with these treatments.
Overall, the potential of medical cannabis for neuroprotection is a promising area of research. While more research is needed to fully understand its mechanisms and effects, cannabis-based treatments have shown potential as a therapeutic tool in the management of neurodegenerative diseases. As with any medical treatment, it is important for patients to discuss the potential benefits and risks with their healthcare provider and to make informed decisions about their care.
Research on medical cannabis and its role in Neuroprotection
1. Cannabidiol, neuroprotection and neuropsychiatric disorders
Abstract
Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa. It has possible therapeutic effects over a broad range of neuropsychiatric disorders. CBD attenuates brain damage associated with neurodegenerative and/or ischemic conditions. It also has positive effects on attenuating psychotic-, anxiety- and depressive-like behaviors. Moreover, CBD affects synaptic plasticity and facilitates neurogenesis. The mechanisms of these effects are still not entirely clear but seem to involve multiple pharmacological targets. In the present review, we summarized the main biochemical and molecular mechanisms that have been associated with the therapeutic effects of CBD, focusing on their relevance to brain function, neuroprotection and neuropsychiatric disorders.
2. Cannabidiol and (−)Δ9-tetrahydrocannabinol are neuroprotective antioxidants
Abstract
The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (−)Δ9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-D-aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or α-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.
3. Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on β-amyloid-induced toxicity in PC12 cells
Abstract
Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of β-amyloid peptide aggregates. Here, we studied the effect of cannabidiol, a major non-psychoactive component of the marijuana plant (Cannabis sativa) on β-amyloid peptide-induced toxicity in cultured rat pheocromocytoma PC12 cells. Following exposure of cells to β-amyloid peptide (1 µg/mL), a marked reduction in cell survival was observed. This effect was associated with increased reactive oxygen species (ROS) production and lipid peroxidation, as well as caspase 3 (a key enzyme in the apoptosis cell-signalling cascade) appearance, DNA fragmentation and increased intracellular calcium. Treatment of the cells with cannabidiol (10−7−10−4m) prior to β-amyloid peptide exposure significantly elevated cell survival while it decreased ROS production, lipid peroxidation, caspase 3 levels, DNA fragmentation and intracellular calcium. Our results indicate that cannabidiol exerts a combination of neuroprotective, anti-oxidative and anti-apoptotic effects against β-amyloid peptide toxicity, and that inhibition of caspase 3 appearance from its inactive precursor, pro-caspase 3, by cannabidiol is involved in the signalling pathway for this neuroprotection.
4. Repeated treatment with cannabidiol but not Δ9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance
Abstract
Both Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol are known to have a neuroprotective effect against cerebral ischemia. We examined whether repeated treatment with both drugs led to tolerance of their neuroprotective effects in mice subjected to 4 h-middle cerebral artery (MCA) occlusion. The neuroprotective effect of Δ9-THC but not cannabidiol was inhibited by SR141716, cannabinoid CB1 receptor antagonist. Fourteen-day repeated treatment with Δ9-THC, but not cannabidiol, led to tolerance of the neuroprotective and hypothermic effects. In addition, repeated treatment with Δ9-THC reversed the increase in cerebral blood flow (CBF), while cannabidiol did not reverse that effect. Repeated treatment with Δ9-THC caused CB1 receptor desensitization and down-regulation in MCA occluded mice. On the contrary, cannabidiol did not influence these effects. Moreover, the neuroprotective effect and an increase in CBF induced by repeated treatment with cannabidiol were in part inhibited by WAY100135, serotonin 5-HT1A receptor antagonist. Cannabidiol exhibited stronger antioxidative power than Δ9-THC in an in vitro study using the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical. Thus, cannabidiol is a potent antioxidant agent without developing tolerance to its neuroprotective effect, acting through a CB1 receptor-independent mechanism. It is to be hoped that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.