Derivatives Of Cannabis Sativa Research Articles

Phytochemical Constituents and Derivatives of Cannabis sativa; Bridging the Gap in Melanoma Treatment.

Melanoma is deadly, physically impairing, and has ongoing treatment deficiencies. Current treatment regimens include surgery, targeted kinase inhibitors, immunotherapy, and combined approaches. Each of these treatments face pitfalls, with diminutive five-year survival in patients with advanced metastatic invasion of lymph and secondary organ tissues. Polyphenolic compounds, including cannabinoids, terpenoids, and flavonoids; both natural and synthetic, have emerging evidence of nutraceutical, cosmetic and pharmacological potential, including specific anti-cancer, anti-inflammatory, and palliative utility. Cannabis sativa is a wellspring of medicinal compounds whose direct and adjunctive application may offer considerable relief for melanoma suffers worldwide. This review aims to address the diverse applications of C. sativa's biocompounds in the scope of melanoma and suggest it as a strong candidate for ongoing pharmacological evaluation.

Effectiveness of epilepsy treatment with Cannabis Sativa derivatives in children with Dravet Syndrome – Systematic Review (P1-1.Virtual)

Effectiveness of epilepsy treatment with Cannabis Sativa derivatives in children with Dravet Syndrome – Systematic Review (P1-1.Virtual)

Cannabis sativa as a Treatment for Obesity: From Anti-Inflammatory Indirect Support to a Promising Metabolic Re-Establishment Target.

Introduction: Obesity is defined as an excess of accumulation of fat that can be harmful to health. Storage of excess fat in the adipose tissue triggers an inflammatory process, which makes obesity a low-grade chronic inflammatory disease. Obesity is considered a complex and multifactorial disease; hence, no intervention strategy appears to be an ideal treatment for all individuals. Therefore, new therapeutic alternatives are often studied for the treatment of this disease. Currently, herbal medicines are gaining ground in the treatment of obesity and its comorbidities. In this context, much attention is being paid to Cannabis sativa derivatives, and their therapeutic functions are being widely studied, including in treating obesity. Objective: Highlight the pharmacological properties of Δ9-tetrahydrocannabivarin (THCV), Δ9-tetrahydrocannabidinol (THC), and cannabidiol (CBD), the predominant isolated components of Cannabis sativa, as well as its therapeutic potential in the treatment of obesity. Methods: This is a narrative review that shows the existing scientific evidence on the clinical application of Cannabis sativa as a possible treatment for obesity. Data collection was performed in the PubMed electronic database. The following word combinations were used: Cannabis and obesity, Cannabis sativa and obesity, THCV and obesity, THC and obesity, CBD and obesity, and Cannabis sativa and inflammation. Results: Evidence shows that Cannabis sativa derivatives have therapeutic potential due to their anti-inflammatory properties. In addition, people who use cannabis have a lower body mass index than those who do not, making the plant an option to reduce and reverse inflammation and comorbidities in obesity. Conclusion: It is concluded that phytocannabinoids derived from Cannabis sativa have therapeutic potential due to its anti-inflammatory, antioxidant, and neuroprotective properties, making the plant a study option to reduce and reverse inflammation and comorbidities associated with obesity.

Therapeutic use of medicinal cannabis in difficult to manage epilepsy.

Intractable epilepsy is currently defined by the International League Against Epilepsy as failure of adequate trials of two tolerated and appropriately chosen antiepileptic drugs (AED) to achieve sustained seizure freedom 1. Approximately 33% of adults and 20% of children with epilepsy meet that definition 2. This is despite the fact that there are 25 registered AED with a particular explosion of new drugs over the past 3 decades. That increased number of drugs surprisingly has not led to a significant reduction in the proportion of people who have intractable epilepsy. Thus, there was great hope in the epilepsy community (mainly patients and their families) that medicinal cannabis would bridge this gap. Cannabis had been used for millennia (especially in Asia) to treat a great variety of ailments including epilepsy. In the 19th century, its use became more mainstream in the western world with several neurologists documenting its efficacy and safety in small case series 3. Used alone or in combination with other treatments such as bromide, cannabinoids were the mainstay of epilepsy treatment until the development of phenobarbital (1912) and phenytoin (1937), which were proven to be efficacious. So why the recent resurgence of interest? A combination of the power of the Internet, vested interests such as agri‐business and marijuana legalization groups and growing public distrust of institutions and science 4. One just has to search the internet for ‘epilepsy and cannabis’ and often the same individual cases are recycled as examples of the next miracle cannabis cure of epilepsy. This Internet‐magnified confirmation bias of anecdotal reports has polarized views, bred distrust of doctors (and their requirement for evidence‐based medicine) and provided considerable hope but minimal help to those suffering with epilepsy and their carers. This review will focus mainly on cannabidiol (CBD), the most researched compound of the Cannabis sativa derivatives.

Neuroanatomical substrates involved in cannabinoid modulation of defensive responses

Administration of Cannabis sativa derivatives causes anxiolytic or anxiogenic effects in humans and laboratory animals, depending on the specific compound and dosage used. In agreement with these findings, several studies in the last decade have indicated that the endocannabinoid system modulates neuronal activity in areas involved in defensive responses. The mechanisms of these effects, however, are still not clear. The present review summarizes recent data suggesting that they involve modulation of glutamate and GABA-mediated neurotransmission in brain sites such as the medial prefrontal cortex, amygdaloid complex, bed nucleus of the stria terminalis, hippocampus and dorsal periaqueductal gray. Moreover, we also discuss results indicating that, in these regions, the endocannabinoid system could be particularly engaged by highly stressful situations.

An Overview on the Biochemistry of the Cannabinoid System

About 40 years ago, cannabinoids were considered as the substances responsible for the psychoactive properties of marijuana and other derivatives of Cannabis sativa, whereas their medicinal use remained unexplored. However, with the discovery of the endocannabinoid system 20 years later, the compounds able to modify this system are being reconsidered for their therapeutic potential. Thus, the term "cannabinoid" includes now much more compounds than those present in C. sativa derivatives, for instance, numerous synthetic cannabinoids obtained by modifications from plant-derived cannabinoids or from the compounds that behave as endogenous ligands for the different cannabinoid receptor types. The term "cannabinoid" should also refer to some prototypes of selective antagonists for these receptors. The explanation for this exponential growth in cannabinoid pharmacology is the discovery and characterization of the endocannabinoid signaling system (receptors, ligands, and inactivation system) which plays a modulatory role mainly in the brain but also in the periphery. The objective of the present review article was to give an overview of the present state-of-the-art of biochemistry of the endocannabinoid system. Other authors in this volume will review their functions in the brain, their alterations in a variety of neurological and psychiatric pathologies, and the proposed therapeutic benefits in these diseases of new cannabinoid-related compounds that improve the pharmacological properties of classic cannabinoids.

How many sites of action for endocannabinoids to control energy metabolism?

The promising results obtained by clinical trials using Rimonabant to tackle visceral obesity and related disorders recently promoted a remarkable impulse to carry out detailed investigations into the mechanisms of action of endocannabinoids in regulating food intake and energy metabolism. The endocannabinoid system has been known for many years to play an important role in the modulation of the neuronal pathways mediating the rewarding properties of food. However, in the last few years, with the advanced understanding of the crucial role of the hypothalamic neuronal network in the regulation of appetite, several studies have also directed attention to the orexigenic role of the endocannabinoid system, substantiating the well known appetite stimulating properties of derivatives of Cannabis sativa. Furthermore, the last 2 years have seen a number of relevant publications emphasizing the role of endocannabinoids as significant players in various peripheral metabolic processes. To date, the roles of the endocannabinoid system in influencing energy metabolism have proved to be more complex than was formerly believed. However, the diverse ability to modulate both central and peripheral processes highlights the pivotal involvement of the endocannabinoid system in the control of metabolic processes. This review describes the roles of endocannabinoids and the cannabinoid type 1 receptor (CB1) in the control of energy balance.

Therapeutic Potential of the Endocannabinoid System in the Brain

Cannabinoids have been predominantly considered as the substances responsible of the psychoactive properties of marijuana and other derivatives of Cannabis sativa. However, these compounds are now being also considered for their therapeutic potential, since the term "cannabinoid" includes much more compounds than those present in Cannabis sativa derivatives. Among them, there are numerous synthetic cannabinoids obtained by modifications from plant-derived cannabinoids, but also from the compounds that behave as endogenous ligands for the different cannabinoid receptor subtypes. Within the family of "cannabinoid-related compounds", one should also include some prototypes of selective antagonists for these receptors, and also the recently developed inhibitors of the mechanism of finalization of the biological action of endocannabinoids (transporter + FAAH). All this boom of the cannabinoid pharmacology has, therefore, an explanation in the recent discovery and characterization of the endocannabinoid signaling system, which plays a modulatory role mainly in the brain but also in the periphery. The objective of the present article will be to review, from pharmacological and biochemical points of view, the more recent advances in the study of the endocannabinoid system and their functions in the brain, as well as their alterations in a variety of pathologies and the proposed therapeutic benefits of novel cannabinoid-related compounds that improve the pharmacokinetic and pharmacodynamic properties of classic cannabinoids.

Endocannabinoids: getting the message across.

The endocannabinoids have emerged as important intercellular signals in the nervous system. The fatty acid amide arachidonylethanolamide (anandamide) is the prototypical endocannabinoid, i.e., an endogenous ligand of the G protein-coupled cannabinoid receptor in the brain, CB1, which binds the main psychoactive component of marijuana and other derivatives of Cannabis sativa (1). After a rise in intracellular calcium or activation of certain neurotransmitter receptors, endocannabinoids are synthesized by cleavage of phospholipid precursors that are present in cellular membranes (2). They often act as retrograde messengers, emanating from morphologically undifferentiated regions of postsynaptic principal cells and traveling backwards across synapses, where they transiently inhibit the release of either the inhibitory neurotransmitter γ-aminobutyric acid (GABA) or the excitatory transmitter glutamate (see Fig. 1 and ref. 3 for a review). This powerful influence on synaptic transmission enables the endocannabinoids to help regulate behaviors, such as feeding (4), fear (5), and anxiety (6). Fig. 1. Retrograde signaling by endocannabinoids. The endocannabinoids anandamide and 2-AG are synthesized in postsynaptic target cells such as hippocampal pyramidal cells (right). Synthesis is initiated by calcium influx through voltage-gated calcium channels, or by the activation of G protein-coupled neurotransmitter receptors, including type I metabotropic glutamate receptors (mGluR) or muscarinic acetylcholine receptors (mAChR) (3). The endocannabinoids gain access to the extracellular space and activate CB1 cannabinoid receptors found concentrated on certain nerve terminals, e.g., of cholecystokinin-containing GABAergic interneurons in hippocampus (2). CB1 activation causes presynaptic inhibition of GABA or glutamate release by inhibiting calcium channels, interfering with vesicle release, and activating potassium channels. The endocannabinoids are taken up into postsynaptic or presynaptic cells by the anandamide transporter (AT). The degradative enzyme FAAH is present in postsynaptic cells, and monoglyceride lipase (not shown), which degrades 2-AG, is found in presynaptic terminals (2). As is true of other intercellular messengers, the time course …

Cannabis: a pot of cellular actions in the mesolimbic system

The mesolimbic and mesocortical dopamine system, particularly the nucleus accumbens (NAc), is involved in the reinforcing properties of several drugs of abuse, including cocaine, amphetamines, opioids, nicotine and alcohol. These drugs are thought to produce their reinforcing effects by altering dopamine release within the NAc. Derivatives of Cannabis sativa, such as marijuana and hashish, are also major drugs of abuse. The main psychoactive ingredient of cannabis, Δ9-tetrahydrocannabinol (THC) acts on cannabinoid CB1 receptors in the brain. Although CB1 receptor activation has been shown to alter dopamine release within the NAc, there is some controversy over the reinforcing nature of cannabis and whether it acts as a gateway drug.