Posts Tagged tetrahydrocannabinol

[Abstract + References] Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy

Abstract

Cannabidiol (CBD) is a major active component of the Cannabis plant, which, unlike tetrahydrocannabinol (THC), is devoid of euphoria-inducing properties. During the last 10 years, there has been increasing interest in the use of CBD-enriched products for the treatment of epilepsy. In 2018, an oil-based highly purified liquid formulation of CBD (Epidiolex) derived from Cannabis sativa was approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). The mechanisms underlying the antiseizure effects of CBD are unclear but may involve, among others, antagonism of G protein-coupled receptor 55 (GPR55), desensitization of transient receptor potential of vanilloid type 1 (TRPV1) channels, and inhibition of adenosine reuptake. CBD has complex and variable pharmacokinetics, with a prominent first-pass effect and a low oral bioavailability that increases fourfold when CBD is taken with a high-fat/high-calorie meal. In four randomized, double-blind, parallel-group, adjunctive-therapy trials, CBD given at doses of 10 and 20 mg/kg/day administered in two divided administrations was found to be superior to placebo in reducing the frequency of drop seizures in patients with LGS and convulsive seizures in patients with DS. Preliminary results from a recently completed controlled trial indicate that efficacy also extends to the treatment of seizures associated with the tuberous sclerosis complex. The most common adverse events that differentiated CBD from placebo in controlled trials included somnolence/sedation, decreased appetite, increases in transaminases, and diarrhea, behavioral changes, skin rashes, fatigue, and sleep disturbances. About one-half of the patients included in the DS and LGS trials were receiving concomitant therapy with clobazam, and in these patients a CBD-induced increase in serum levels of the active metabolite norclobazam may have contributed to improved seizure outcomes and to precipitation of some adverse effects, particularly somnolence.

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[REVIEW] Epilepsy and Cannabis: A Literature Review – Full Text PDF

Abstract

Epilepsy is considered to be one of the most common non-communicable neurological diseases especially in low to middle-income countries. Approximately one-third of patients with epilepsy have seizures that are resistant to antiepileptic medications. Clinical trials for the treatment of medically refractory epilepsy have mostly focused on new drug treatments, and result in a significant portion of subjects whose seizures remain refractory to medication. The off-label use of cannabis sativa plant in treating seizures is known since ancient times. The active ingredients of this plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the latter considered safer and more effective in treating seizures, and with less adverse psychotropic effects.

Clinical trials prior to two years ago have shown little to no significant effects of cannabis in reducing seizures. These trials seem to be underpowered, with a sample size less than 15. In contrast, more recent studies that have included over 100 participants showed that CBD use resulted in a significant reduction in seizure frequency. Adverse effects of CBD overall appear to be benign, while more concerning adverse effects (e.g., elevated liver enzymes) improve with continued CBD use or dose reduction.

In most of the trials, CBD is used in adjunct with epilepsy medication, therefore it remains to be determined whether CBD is itself antiepileptic or a potentiator of traditional antiepileptic medications. Future trials may evaluate the efficacy of CBD in treating seizures due to specific etiologies (e.g., post-traumatic, post-stroke, idiopathic).[…]

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[WEB SITE] Medical Marijuana for Epilepsy: What We Know

Rahul Guha, MD, July 26, 2018

Earlier this year, the Virginia State Legislature voted to expand the medical cannabis oil program in the Commonwealth. I have patients ask me about medical marijuana during every clinic visit. Here are a few talking points that will help guide the discussion with your patients.

Patients usually start the conversation by saying, “I read on my cousin’s Facebook wall that smoking marijuana can treat my epilepsy.”

Let’s take a step back and talk about the clinically important compounds in marijuana. The first is tetrahydrocannabinol (THC). It exerts its effect through a pair of G protein-coupled cannabinoid receptors named, conveniently, CB1 and CB2. The effect of THC on synapses produces the typical “high” that allows you to tolerate 11-minute guitar solos and most items on Taco Bell’s late-night menu. Early animal models showed mixed effects of THC on epilepsy and, in some cases, worsening seizures. This is different from cannabidiol (CBD), which interacts with a variety of other receptors. More promising effects reported in early animal models and anecdotal evidence from case reports spurred the movement towards clinical trials measuring the effect of CBD on epilepsy.

Will medical marijuana help my epilepsy?

We don’t know which epilepsy syndromes are most responsive to CBD. We don’t know the long-term effects of CBD or THC in the brains of patients with epilepsy. We have not agreed on the best dosing strategy for these medications. The best evidence for CBD in epilepsy comes from two recently published trials studying the effect of the drug in patients with Lennox-Gastaut syndrome and Dravet syndrome.[1,2] These diseases develop in childhood or infancy due to underlying genetic changes and are resistant to treatment.

In the studies, patients who were taking an average of six other antiepileptic medications received CBD as an add-on therapy to conventional medications. At 3 months’ follow-up, patients who received the CBD experienced a statistically significant decrease in average seizure frequency compared with placebo.

Can I use commercially available CBD?

Unfortunately, many of the products that are available online or over the counter at your local vape shop are not consistent with labeling. Simply put, there’s no guarantee that you are getting what’s advertised. In addition to unknown dosing and concentrations of THC and CBD, there is a possibility of contaminants, such as pesticides or other drugs, in the product. We can only guarantee the safety and efficacy of US Food and Drug Administration (FDA)-approved products.

How will CBD affect my other medications?

CBD is metabolized by the liver and inhibits cytochrome P450 (CYP) isoenzymes. This inhibition leads to increased levels of topiramate, zonisamide, eslicarbazepine, rufinamide, clobazam, and valproic acid.

Is it legal?

The FDA recently approved a CBD formulation, but there is currently no formulation of CBD that can be prescribed with a Drug Enforcement Administration (DEA) license. Under federal law, cannabis is still considered a Schedule I drug. It is only available through clinical trials and rare compassionate-use exceptions. Patients and providers should familiarize themselves with local laws before recommending CBD for the treatment of epilepsy.

 

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[WEB SITE] Cannabis Oil for Epilepsy – What You Need to Know

Cannabis Oil for Epilepsy – What You Need to KnowCredit: Pixabay

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[ARTICLE] Endocannabinoids: Windows to the Brain – Full Text HTML

Endocannabinoids: Windows to the Brain

Katherine H. Taber, Ph.D. and Robin A. Hurley, M.D.

Cannabis with R/XCannabis sativa (hemp) is a flowering annual that has been in use as a structural material (cordage, cloth, paper) and in medicine for thousands of years.5–7 Reference to the psychoactive effects of its phytochemical products have been found in writing throughout the ancient world. Cannabis herb (marijuana) is made by drying the leaves and flowering tops. Cannabis resin (hashish) is made by collecting the fluid secreted by the plant during the flowering phase.

A recent review indicates that studies of this plant have identified more than 500 compounds within the plant.6 The principle psychoactive cannabinoids in Cannabis sativa are 8 and 9 tetrahydrocannabinol (THC)6,7 9 THC is considered the major psychoactive constituent as it is considerably more abundant in the plant and more potent in effect. The amount of 9 THC varies greatly across plant strains and is also affected by farming and preparation techniques.8Studies suggest an increasing content of 9 THC in street cannabis over the past few decades (e.g., 1.5% in 1980, 4.47% in 1997, 5.11% in 2002).8 9 THC is converted to 11-hydroxy-9 THC in the lungs and liver.7 Onset of action depends on both dose and method of administration. Following ingestion by smoking, initial effects may appear within the first minute, whereas following oral ingestion first effects may appear in 15–30 minutes.8,9 Onset, duration and nature of action (pleasant versus unpleasant) are affected by other factors, as well, such as individual differences in absorption, method of smoking, previous history, anxiety level, and environmental context.8,10Early acute effects commonly include light-headedness and euphoria, with some individuals experiencing tachycardia and hypotension. Later acute effects may include time dilation, relaxation, increased body awareness, increased appetite, sleepiness, impaired memory, and impaired concentration.7–9,11 Adverse reactions do occur (e.g., anxiety, panic, paranoia, psychotic symptoms), but are much less common.8,9,11,12 Functional imaging studies indicate that intoxication is associated with increased regional cerebral blood flow and metabolism, particularly in frontal and limbic regions as well as the cerebellum.8

Both tolerance and dependence can develop with chronic use.9,11–13 Withdrawal is characterized by nervousness, tension, anxiety, and sleep disturbances. While long-term cognitive impairment has been reported in some studies, the evidence for this is not strong.7–9,11,12 Some studies support an influence of cannabis use on the development of psychiatric disorders, particularly schizophrenia and mood disorders.11,12,14

A surge in research into the mechanism of action for 9 THC in the brain followed its isolation and identification in the 1960s.6 This led to the identification of endogenous cannabinoid (endocannabinoid) receptors in brain tissue. Research intensified following the cloning of these receptors (CB1 and CB2) in the early 1990s.6,7,15,16 Identification of the first endocannabinoid, N-arachidonoylethanolamine (anandamide, from the Sanskrit for “eternal bliss”) was achieved soon after.6 A decade later the modulatory action of endocannabinoids at synapses was discovered.17 Both the CB1 and CB2 receptors are cell surface proteins that span the membrane and are coupled intracellularly to one of the G-proteins.7,16–18 The distributions and actions of the CB1 and CB2 receptors are quite different.6,7,9,15–19 CB1 receptors are located predominately on axon terminals in both the central and peripheral nervous system and on some peripheral tissues (e.g., liver, gut, adrenal, muscle, fat). CB2 receptors are found principally peripherally on immune cells (e.g., spleen, macrophages, tonsils, monocytes, neutrophils), and were originally not thought to occur in the brain. More recently they have been identified on both neurons and glial cells, where they may participate in immune functions.6,7,9,17,20–22 This article will focus on the CB1 receptor and compounds that interact with it, as this system mediates most or all of the psychotropic actions of cannabinoids.

Continue —>  Endocannabinoids: Windows to the Brain | Cannabis As Medicine.

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