“Cannabis sativa active compounds are extensively studied for their therapeutic effects, beyond the well-known psychotropic activity. C. Sativa is used to treat different medical indications, such as multiple sclerosis, spasticity, epilepsy, ulcerative colitis and pain. Simultaneously, basic research is discovering new constituents of cannabis-derived compounds and their receptors capable of neuroprotection and neuronal activity modulation. The function of the various phytochemicals in different therapeutic processes is not fully understood, but their significant role is starting to emerge and be appreciated. In this review, we will consider the structure-activity relationship (SAR) of cannabinoid compounds able to bind to cannabinoid receptors and act as therapeutic agents in neuronal diseases, e.g., Parkinson’s disease.” https://www.ncbi.nlm.nih.gov/pubmed/29941830 http://www.mdpi.com/1420-3049/23/7/1526]]>
Category Archives: Epilepsy
The adult motor phenotype of Dravet syndrome is associated with mutation of the STXBP1 gene and responds well to cannabidiol treatment.
“Dravet syndrome is a terrible disease generally caused by mutations of the SCN1A gene. Recently others genes such as STXBP1 have been involved in the pathogenesis of the disease. The STXBP1 mutation in patients with Dravet Syndrome may additionally causes several parkinsonian features usually attributed to carriers of the SCN1A mutation. Management continues to be difficult that is why Cannabidiol emerged as valid option for treatment of this condition.” https://www.ncbi.nlm.nih.gov/pubmed/29929108 https://www.seizure-journal.com/article/S1059-1311(17)30500-9/fulltext]]>
Investigational cannabinoids in seizure disorders, what have we learned thus far?
“The anticonvulsant activity of cannabinoids attracted much attention in the last decade. Cannabinoids that are currently investigated with the intention of making them drugs for the treatment of epilepsy are cannabidiol, cannabidivarin, Δ9-tetrahydrocannabivarin and Δ9-tetrahydrocannabinolic acid.
Areas covered. In this review, the authors look at the results of pre-clinical and clinical studies with investigational cannabinoids. Relevant literature was searched for in MEDLINE, SCOPUS, EBSCO, GOOGLE SCHOLAR and SCINDEX databases.
Expert opinion. Pre-clinical studies confirmed anticonvulsant activity of cannabidiol and cannabidivarin in a variety of epilepsy models. While the results of clinical trials with cannabidivarin are still awaited, cannabidiol showed clear therapeutic benefit and good safety in patients with therapy resistant seizures associated with Dravet syndrome and in patients with Lennox-Gastaut syndrome who have drop seizures. However, the full therapeutic potential of cannabinoids in treatment-resistant epilepsy needs to be investigated in the near future.”
https://www.ncbi.nlm.nih.gov/pubmed/29842819
https://www.tandfonline.com/doi/abs/10.1080/13543784.2018.1482275
Endocannabinoid CB1 receptors are involved in antiepileptogenic effect of low frequency electrical stimulation during perforant path kindling in rats.
“Administration of low-frequency electrical stimulation (LFS) at the kindling site has an antiepileptogenic effect. In the present study, we investigated the role of cannabinoid receptors type 1 (CB1) in mediating the inhibitory effects of LFS on the development of perforant path kindled seizures.
RESULTS:
Application of LFS had inhibitory effect on development of kindled seizures (kindling rate). Microinjection of AM281 (0.5 μg/μl) immediately after the last kindling stimulation (before LFS application) reduced the inhibitory effect of LFS on the kindling rate and suppressed the effects of LFS on potentiation (increasing the magnitude) of both population spike amplitude and population excitatory postsynaptic potential slope during kindling acquisition. AM281 pretreatment also prevented the effects of LFS on kindling-induced increase in early and late paired pulse depression. The higher dose of AM281 (2 μg/μl) failed to exert the effects observed with its lower dose (0.5 μg/μl). In addition, there was a decreased CB1 receptors immunostaining in kindled animals compared to control. However, application of LFS following kindling stimulations led to overexpression of CB1 receptors in the dentate gyrus.CONCLUSION:
Obtained results showed that activation of overexpressed cannabinoid CB1 receptors by endogenous cannabinoids may have a role in mediating the inhibitory effect of LFS on perforant path kindled seizures.” https://www.ncbi.nlm.nih.gov/pubmed/29800824 https://www.sciencedirect.com/science/article/pii/S0920121117304291?via%3Dihub]]>Review of the neurological benefits of phytocannabinoids.
“Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS.
METHODS:
In 1980, Cunha et al. reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts.RESULTS:
Recent neurological uses include adjunctive treatment for malignant brain tumors, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, neuropathic pain, and the childhood seizure disorders Lennox-Gastaut and Dravet syndromes. In addition, psychiatric and mood disorders, such as schizophrenia, anxiety, depression, addiction, postconcussion syndrome, and posttraumatic stress disorders are being studied using phytocannabinoids.CONCLUSIONS:
In this review we will provide animal and human research data on the current clinical neurological uses for CBD individually and in combination with Δ9-THC. We will emphasize the neuroprotective, antiinflammatory, and immunomodulatory benefits of phytocannabinoids and their applications in various clinical syndromes.” https://www.ncbi.nlm.nih.gov/pubmed/29770251 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938896/]]>Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome.
“Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy. Among children and adults with the Lennox-Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo.” https://www.ncbi.nlm.nih.gov/pubmed/29768152 https://www.nejm.org/doi/10.1056/NEJMoa1714631]]>
Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling
“Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.” https://link.springer.com/article/10.1007/s00018-018-2834-8 http://www.x-mol.com/paper/661834]]>
Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents – An observational, longitudinal study.
“The objective of this observational study was to evaluate the efficacy of medical cannabis for the treatment of refractory epilepsy.
Fifty-seven patients (age 1-20 years) with epilepsy of various etiologies were treated with Cannabis oil extract (CBD/THC ratio of 20:1) for at least 3 months (Median follow up time-18 months). Forty-Six Patients were included in the efficacy analysis. Average CBD dose was11.4 mg/kg/d.
Twenty-six patients (56%) had ≤50% reduction in mean monthly seizure frequency. There was no statistically significant difference in response rate among various epilepsy etiologies, and cannabis strain used.
Younger age at treatment onset (<10 years) and higher CBD dose (>11 mg/kg/d) were associated with better response to treatment. Adverse reactions were reported in 46% of patients and were the main reason for treatment cessation.
Our results suggest that adding CBD-enriched cannabis extract to the treatment regimen of patients with refractory epilepsy may result in a significant reduction in seizure frequency according to parental reports.”
“Research on the antiepileptic effects of (endo-)