“The changing legal landscape including medicinal and recreational consumption of Cannabis sativa has led to renewed interest to study the chemistry and biology of cannabinoids. The chemistry in this chapter highlights approaches to cannabinoid total synthesis with an emphasis on the implementation of modern methods and tactics, which provide access to modified structures and enable investigations of the biology of the cannabinoid product family.” https://www.ncbi.nlm.nih.gov/pubmed/28120230
“This study assessed whether oral administration of delta-9-tetrahydrocannbinol (THC) effectively suppressed cannabis withdrawal in an outpatient environment.
The primary aims were to establish the pharmacological specificity of the withdrawal syndrome and to obtain information relevant to determining the potential use of THC to assist in the treatment of cannabis dependence.
Eight adult, daily cannabis users who were not seeking treatment participated in a 40-day, within-subject ABACAD study. Participants administered daily doses of placebo, 30 mg (10 mg/tid), or 90 mg (30 mg/tid) oral THC during three, 5-day periods of abstinence from cannabis use separated by 7-9 periods of smoking cannabis as usual.
Comparison of withdrawal symptoms across conditions indicated that (1) the lower dose of THC reduced withdrawal discomfort, and (2) the higher dose produced additional suppression in withdrawal symptoms such that symptom ratings did not differ from the smoking-as-usual conditions. Minimal adverse effects were associated with either active dose of THC.
This demonstration of dose-responsivity replicates and extends prior findings of the pharmacological specificity of the cannabis withdrawal syndrome. The efficacy of these doses for suppressing cannabis withdrawal suggests oral THC might be used as an intervention to aid cannabis cessation attempts.” https://www.ncbi.nlm.nih.gov/pubmed/16769180
“Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report. CBD can be effective for the treatment of cannabis withdrawal syndrome.” https://www.ncbi.nlm.nih.gov/pubmed/23095052
“Oral delta-9-tetrahydrocannabinol suppresses cannabis withdrawal symptoms.” https://www.ncbi.nlm.nih.gov/pubmed/16769180
“Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury.
In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen-glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line.
This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.”
“Complex, and sometimes intractable, seizures affect the quality of life and cognitive development of over 90% of individuals with Wolf-Hirschhorn syndrome (WHS). Fine resolution genotype-phenotype mapping of the WHS locus recently identified a candidate gene whose probable function has led to insights into a mechanism connecting WHS seizures with those of Dravet syndrome, a distinct condition caused by mutations in SCN1A and SCN1B. In addition to this possible molecular mechanistic connection, these disorders’ seizures share a strikingly similar constellation of features, including clinical presentation, seizure types, early age of onset, EEG pattern, and responses to specific anti-epileptic drugs. Based in part on these similarities, we suggest that a highly successful Phase III clinical trial of a formulation of cannabidiol for Dravet syndrome seizures may be directly translatable into possible benefits for WHS individuals with challenging seizure patterns.”
“The identification and cloning of the two major cannabinoid (CB1 and CB2) receptors together with the discovery of their endogenous ligands in the late 80s and early 90s, resulted in a major effort aimed at understanding the mechanisms and physiological roles of the endocannabinoid system (ECS). Due to its expression and localization in the central nervous system (CNS), the CB1 receptor together with its endogenous ligands (endocannabinoids (eCB)) and the enzymes involved in their synthesis and degradation, has been implicated in multiple pathophysiological events ranging from memory deficits to neurodegenerative disorders among others. In this review, we will provide a general overview of the ECS with emphasis on the CB1 receptor in health and disease. We will describe our current understanding of the complex aspects of receptor signaling and trafficking, including the non-canonical signaling pathways such as those mediated by β-arrestins within the context of functional selectivity and ligand bias. Finally, we will highlight some of the disorders in which CB1 receptors have been implicated. Significant knowledge has been achieved over the last 30 years. However, much more research is still needed to fully understand the complex roles of the ECS, particularly in vivo and to unlock its true potential as a source of therapeutic targets.”
“The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain.
Our data provide evidence that CB2 receptor function emerges in the RVM in persistent inflammation and that selective CB2 receptor agonists may be useful for treatment of persistent inflammatory pain.
These studies demonstrate that endocannabinoid signaling to CB1 and CB2 receptors in adult rostral ventromedial medulla is altered in persistent inflammation. The emergence of CB2 receptor function in the rostral ventromedial medulla provides additional rationale for the development of CB2 receptor-selective agonists as useful therapeutics for chronic inflammatory pain.”
“Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant.
In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA).
Despite its status, there are no well-controlled data available regarding its abuse liability.
Overall, CBD did not display any signals of abuse liability at the doses tested and these data may help inform U.S. regulatory decisions regarding CBD schedule on the CSA.”
“Cannabinoids have intraocular pressure (IOP) lowering effects, thus, they have a therapeutic potential in the treatment of glaucoma.
Our aim was to develop a safer, cannabinoid type anti-glaucoma agent, a topically applied soft analogue, that has local, but no systemic effect.
The lead compound chosen was a nitrogen-containing cannabinoid analogue that was shown to have IOP lowering activity.
A full library of possible soft drugs was generated and the structures were ranked based on the closeness of calculated properties to those of the lead compound.
The lead compound has been synthesized, and a preliminary pharmacological study was performed.
The structure-activity relationship and pharmacological results indicate a good possibility for the development of a safe, soft anti-glaucoma agent.”
“The leading cause of irreversible blindness is glaucoma, a disease normally characterized by the development of ocular hypertension and consequent damage to the optic nerve at its point of retinal attachment. This results in a narrowing of the visual field, and eventually results in blindness.
A number of drugs are available to lower intraocular pressure (IOP), but, occasionally, they are ineffective or have intolerable side-effects for some patients and can lose efficacy with chronic administration.
The smoking of marijuana has decreased IOP in glaucoma patients. Cannabinoid drugs, therefore, are thought to have significant potential for pharmaceutical development.
The discovery of ocular cannabinoid receptors implied an explanation for the induction of hypotension by topical cannabinoid applications, and has stimulated a new phase of ophthalmic cannabinoid research.
Featured within these investigations is the possibility that at least some cannabinoids may ameliorate optic neuronal damage through suppression of N-methyl-D-aspartate receptor hyperexcitability, stimulation of neural microcirculation, and the suppression of both apoptosis and damaging free radical reactions, among other mechanisms.
Separation of therapeutic actions from side-effects now seems possible through a diverse array of novel chemical, pharmacological, and formulation strategies.”
“In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract.
Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors.
After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS.
The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.”
