

“Δ9-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain.
The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain.
Low blood THC levels of <1 ng/ml corresponded to an increased glucose uptake while blood THC levels > 10 ng/ml coincided with a decreased glucose uptake. The effective concentration in this region was estimated 2.4 ng/ml.
This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose – an effect that may be of relevance in behavioural studies.”
https://www.ncbi.nlm.nih.gov/pubmed/28219717]]>
“Cannabinoids, the constituents of the marijuana plant and their analogs, have not only neurobehavioral but also cardiovascular effects. Great advances in the last couple of decades have led to better understanding of the physiological effects of the cannabinoids and of their role in various cardiovascular pathologies. The potential therapeutic use of cannabinoids in various cardiac diseases, such as ischemic injury, heart failure, and cardiac arrhythmias, has been studied in animal models. The purpose of this article is to review the physiological cardiovascular properties of cannabinoids and to summarize the knowledge related to their potential therapeutic use.” https://www.ncbi.nlm.nih.gov/pubmed/20946323
“Whereas the cannabis plant has a long history of medicinal use, it is only in recent years that a sufficient understanding of the pharmacology of the main plant constituents has allowed for a better understanding of the most rational therapeutic targets.
The distribution of cannabinoid receptors, both within the nervous system and without, and the development of pharmacological tools to investigate their function has lead to a substantial increase in efforts to develop cannabinoids as therapeutic agents.
Concomitant with these efforts, the understanding of the pharmacology of plant cannabinoids at receptor and other systems distinct from the cannabinoid receptors suggests that the therapeutic applications of plant-derived cannabinoids (and presumably their synthetic derivatives also) may be diverse.
This review aims to discuss the clinical evidence investigating the use of medicines derived, directly or indirectly, from plant cannabinoids with special reference to neurological disorders.
Published studies suggest that the oral administration of cannabinoids may not be the preferred route of administration and that plant extracts show greater evidence of efficacy than synthetic compounds. One of these, Sativex (GW Pharmaceuticals), was approved as a prescription medicine in Canada in 2005 and is currently under regulatory review in the EU.” https://www.ncbi.nlm.nih.gov/pubmed/17952657
“Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. The aim of this report was to provide a short but important overview of evidences that are useful to better characterize the efficacy as well as the molecular pathways modulated by cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/28197175
“The endocannabinoid system in amyotrophic lateral sclerosis. There is increasing evidence that cannabinoids and manipulation of the endocannabinoid system may have therapeutic value in ALS. Cannabinoids exert anti-glutamatergic and anti-inflammatory actions through activation of the CB(1) and CB(2) receptors. The ability of cannabinoids to target multiple neurotoxic pathways in different cell populations may increase their therapeutic potential in the treatment of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/18781981
“Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis (ALS). Our data suggest that cannabinoid CB1 receptors might be potential therapeutic targets for this dramatic disease.” http://www.ncbi.nlm.nih.gov/pubmed/19452308
“Cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis. Cannabinoid CB2 receptor-selective compounds may be the basis for developing new drugs for the treatment of ALS and other chronic neurodegenerative diseases.” http://www.ncbi.nlm.nih.gov/pubmed/16781706
“Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. The cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/15204022
“Δ9-Tetrahydrocannabinol (Δ9-THC) is the main psychoactive constituent in the plant Cannabis sativa (marijuana) and produces its effects by activation of cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) cannabinoid receptors. Administration of the non-selective partial cannabinoid agonists Δ9-THC or cannabinol are successful in delaying motor impairment and prolonging survival in mice after the onset of symptoms. Collectively, these studies suggest that cannabinoid receptors might serve as novel therapeutic targets for ALS drug development. CB2 agonists may slow motor neuron degeneration and preserve motor function, and represent a novel therapeutic modality for treatment of ALS.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819701/
“Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS)” http://www.ncbi.nlm.nih.gov/pubmed/22594565
“Therapeutic options for amyotrophic lateral sclerosis (ALS) remain limited. Evidence suggests that cannabinoids, the bioactive ingredients of marijuana (Cannabis sativa) might have some therapeutic benefit in this disease. We found that this treatment significantly delays disease onset. Cannabinoids might be useful in ameliorating symptoms in ALS.” http://www.ncbi.nlm.nih.gov/pubmed/16183560
“Marijuana is a substance with many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). These include analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction. In addition, marijuana has now been shown to have strong antioxidative and neuroprotective effects. Marijuana should be considered in the pharmacological management of ALS.” http://www.ncbi.nlm.nih.gov/pubmed/11467101
“Ideally, a multidrug regimen would be required to comprehensively address the known pathophysiology of ALS. REMARKABLY, cannabis appears to have activity in all of those areas. Cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. Cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease.” http://www.ncbi.nlm.nih.gov/pubmed/20439484
“In light of the above findings, there is a valid rationale to propose the use of cannabinoid compounds in the pharmacological management of ALS patients. Cannabinoids indeed are able to delay ALS progression and prolong survival.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5270417/
http://www.thctotalhealthcare.com/category/amyotrophic-lateral-sclerosis-als-lou-gehrigs-disease/
“The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. We surveyed the literature for relevant reports of such plant cannabinoid effects and critically reviewed their findings. We found that acute CB1R agonism in simple models of acute seizures in rodents typically produces anti-convulsant effects whereas CB1R antagonists exert converse effects in the same models. However, when the effects of such ligands are examined in more complex models of epilepsy, epileptogenesis and neuroprotection, a less simplistic narrative emerges. Here, the complex interactions between (i) brain regions involved in a given model, (ii) relative contributions of endocannabinoid signaling to modulation of synaptic transmission in such areas, (iii) multi-target effects, (iv) cannabinoid type 1 and type 2 receptor signaling interactions and, (v) timing, (vi) duration and (vii) localization of ligand administration suggest that there is both anti-epileptic therapeutic potential and a pro-epileptic risk in up- and down-regulation of endocannabinoid signaling in the central nervous system. Factors such receptor desensitization and specific pharmacology of ligands used (e.g. full vs partial agonists and neutral antagonists vs inverse agonists) also appear to play an important role in the effects reported. Furthermore, the effects of several plant cannabinoids, most notably cannabidiol (CBD) and cannabidavarin (CBDV), in models of seizures, epilepsy, epileptogenesis, and neuroprotection are less ambiguous, and consistent with reports of therapeutically beneficial effects of these compounds in clinical studies. However, continued paucity of firm information regarding the therapeutic molecular mechanism of CBD/CBDV highlights the continued need for research in this area in order to identify as yet under-exploited targets for drug development and raise our understanding of treatment-resistant epilepsies. The recent reporting of positive results for cannabidiol treatment in two Phase III clinical trials in treatment-resistant epilepsies provides pivotal evidence of clinical efficacy for one plant cannabinoid in epilepsy. Moreover, risks and/or benefits associated with the use of unlicensed Δ9-THC containing marijuana extracts in pediatric epilepsies remain poorly understood. Therefore, in light of these paradigm-changing clinical events, the present review’s findings aim to drive future drug development for newly-identified targets and indications, identify important limitations of animal models in the investigation of plant cannabinoid effects in the epilepsies, and focuses future research in this area on specific, unanswered questions regarding the complexities of endocannabinoid signaling in epilepsy.” https://www.ncbi.nlm.nih.gov/pubmed/28190698]]>
“This work was conducted to prepare β-caryophyllene-hydroxypropyl-β-cyclodextrin inclusion complex (HPβCD/BCP) and investigate its effects and mechanisms on cognitive deficits in vascular dementia (VD) rats.
Overall, the findings demonstrated the protective effects of HPβCD/BCP against cognitive deficits induced by chronic cerebral ischemia and suggested the potential of HPβCD/BCP in the therapy of vascular dementia in the future.”
https://www.ncbi.nlm.nih.gov/pubmed/28154534
“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934
“Nonpsychoactive phytocannabinoids (pCBs) from Cannabis sativa may represent novel therapeutic options for cachexia because of their pleiotropic pharmacological activities, including appetite stimulation.
We have recently shown that purified cannabigerol (CBG) is a novel appetite stimulant in rats.
As standardized extracts from Cannabis chemotypes dominant in one pCB [botanical drug substances (BDSs)] often show greater efficacy and/or potency than purified pCBs, we investigated the effects of a CBG-rich BDS, devoid of psychoactive [INCREMENT]-tetrahydrocannabinol, on feeding behaviour.
CBG-BDS is a novel appetite stimulant, which may have greater potency than purified CBG, despite the absence of [INCREMENT]-tetrahydrocannabinol in the extract.”
https://www.ncbi.nlm.nih.gov/pubmed/28125508
“The remarkable absence of arachidonic acid (AA) in seed plants prompted us to systematically study the presence of C20 polyunsaturated fatty acids, stearic acid, oleic acid, jasmonic acid (JA), N-acylethanolamines (NAEs) and endocannabinoids (ECs) in 71 plant species representative of major phylogenetic clades. Given the difficulty of extrapolating information about lipid metabolites from genetic data we employed targeted metabolomics using LC-MS/MS and GC-MS to study these signaling lipids in plant evolution. Intriguingly, the distribution of AA among the clades showed an inverse correlation with JA which was less present in algae, bryophytes and monilophytes. Conversely, ECs co-occurred with AA in algae and in the lower plants (bryophytes and monilophytes), thus prior to the evolution of cannabinoid receptors in Animalia. We identified two novel EC-like molecules derived from the eicosatetraenoic acid juniperonic acid, an omega-3 structural isomer of AA, namely juniperoyl ethanolamide and 2-juniperoyl glycerol in gymnosperms, lycophytes and few monilophytes. Principal component analysis of the targeted metabolic profiles suggested that distinct NAEs may occur in different monophyletic taxa. This is the first report on the molecular phylogenetic distribution of apparently ancient lipids in the plant kingdom, indicating biosynthetic plasticity and potential physiological roles of EC-like lipids in plants.” https://www.ncbi.nlm.nih.gov/pubmed/28120902]]>
“Cannabis sativa has been used for recreational, therapeutic and other uses for thousands of years.
The plant contains more than 120 C21 terpenophenolic constituents named phytocannabinoids. The Δ9-tetrahydrocannabinol type class of phytocannabinoids comprises the largest proportion of the phytocannabinoid content.
Δ9-tetrahydrocannabinol was first discovered in 1971. This led to the discovery of the endocannabinoid system in mammals, including the cannabinoid receptors CB1 and CB2.
Δ9-Tetrahydrocannabinol exerts its well-known psychotropic effects through the CB1 receptor but this effect of Δ9-tetrahydrocannabinol has limited the use of cannabis medicinally, despite the therapeutic benefits of this phytocannabinoid. This has driven research into other targets outside the endocannabinoid system and has also driven research into the other non-psychotropic phytocannabinoids present in cannabis.
This chapter presents an overview of the molecular pharmacology of the seven most thoroughly investigated phytocannabinoids, namely Δ9-tetrahydrocannabinol, Δ9-tetrahydrocannabivarin, cannabinol, cannabidiol, cannabidivarin, cannabigerol, and cannabichromene.
The targets of these phytocannabinoids are defined both within the endocannabinoid system and beyond.
The pharmacological effect of each individual phytocannabinoid is important in the overall therapeutic and recreational effect of cannabis and slight structural differences can elicit diverse and competing physiological effects.
The proportion of each phytocannabinoid can be influenced by various factors such as growing conditions and extraction methods. It is therefore important to investigate the pharmacology of these seven phytocannabinoids further, and characterise the large number of other phytocannabinoids in order to better understand their contributions to the therapeutic and recreational effects claimed for the whole cannabis plant and its extracts.”
https://www.ncbi.nlm.nih.gov/pubmed/28120231