Tag Archives: cannabidiol

Even High Doses of Oral Cannabidol Do Not Cause THC-Like Effects in Humans

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Mary Ann Liebert, Inc. publishers

“Cannabidiol (CBD) is a cannabinoid of the cannabis plant devoid of intoxicating effects. It may be of therapeutic value in a large number of diseases, including epilepsy, anxiety disorders, depression, schizophrenic psychosis, inflammatory diseases, dystonia, nausea, and vomiting without causing relevant or severe side effects.

No biosynthetic enzyme or pathway exists in the human body to convert CBD to THC.

This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that “the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response.” They issued a warning concerning oral use of CBD and recommend the development of other delivery methods.

However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations.

Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses.”

https://www.ncbi.nlm.nih.gov/pubmed/28861499

http://online.liebertpub.com/doi/full/10.1089/can.2016.0036

“A Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans.”  https://www.ncbi.nlm.nih.gov/pubmed/28861507

The potential role of cannabinoids in epilepsy treatment.

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“Epilepsy is one of the world’s oldest recognized and prevalent neurological diseases. It has a great negative impact on patients’ quality of life (QOL) as a consequence of treatment resistant seizures in about 30% of patients together with drugs’ side effects and comorbidities. Therefore, new drugs are needed and cannabinoids, above all cannabidiol, have recently gathered attention.

This review summarizes the scientific data from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including drugs acting on the endocannabinoid system.

Despite the fact that cannabis has been used for many purposes over 4 millennia, the development of drugs based on cannabinoids has been very slow. Only recently, research has focused on their potential effects and CBD is the first treatment of this group with clinical evidence of efficacy in children with Dravet syndrome; moreover, other studies are currently ongoing to confirm its effectiveness in patients with epilepsy.

On the other hand, it will be of interest to understand whether drugs acting on the endocannabinoid system will be able to reach the market and prove their known preclinical efficacy also in patients with epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/28845714   http://www.tandfonline.com/doi/abs/10.1080/14737175.2017.1373019

 

“The role of cannabinoids and endocannabinoid system in the treatment of epilepsy. Cannabis has been used for thousands of years in the treatment of various diseases. Cannabinoids have been shown in preliminary animal model studies and in studies of patients with epilepsy to have antiepileptic activity. ” https://www.degruyter.com/view/j/joepi.ahead-of-print/joepi-2015-0034/joepi-2015-0034.xml
 
“Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects.”

Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads.

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Advances in Pharmacology

“The golden age of cannabis pharmacology began in the 1960s as Raphael Mechoulam and his colleagues in Israel isolated and synthesized cannabidiol, tetrahydrocannabinol, and other phytocannabinoids. Initially, THC garnered most research interest with sporadic attention to cannabidiol, which has only rekindled in the last 15 years through a demonstration of its remarkably versatile pharmacology and synergy with THC. Gradually a cognizance of the potential of other phytocannabinoids has developed. Contemporaneous assessment of cannabis pharmacology must be even far more inclusive. Medical and recreational consumers alike have long believed in unique attributes of certain cannabis chemovars despite their similarity in cannabinoid profiles. This has focused additional research on the pharmacological contributions of mono- and sesquiterpenoids to the effects of cannabis flower preparations. Investigation reveals these aromatic compounds to contribute modulatory and therapeutic roles in the cannabis entourage far beyond expectations considering their modest concentrations in the plant. Synergistic relationships of the terpenoids to cannabinoids will be highlighted and include many complementary roles to boost therapeutic efficacy in treatment of pain, psychiatric disorders, cancer, and numerous other areas. Additional parts of the cannabis plant provide a wide and distinct variety of other compounds of pharmacological interest, including the triterpenoid friedelin from the roots, canniprene from the fan leaves, cannabisin from seed coats, and cannflavin A from seed sprouts. This chapter will explore the unique attributes of these agents and demonstrate how cannabis may yet fulfil its potential as Mechoulam’s professed “pharmacological treasure trove.””

https://www.ncbi.nlm.nih.gov/pubmed/28826544

http://www.sciencedirect.com/science/article/pii/S1054358917300273?via%3Dihub

Anticonvulsant effect of cannabidiol in the pentylenetetrazole model: Pharmacological mechanisms, electroencephalographic profile, and brain cytokine levels.

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“Cannabidiol (CBD), the main nonpsychotomimetic compound from Cannabis sativa, inhibits experimental seizures in animal models and alleviates certain types of intractable epilepsies in patients.

Here we tested the hypothesis that CBD anticonvulsant mechanisms are prevented by cannabinoid (CB1 and CB2) and vanilloid (TRPV1) receptor blockers. We also investigated its effects on electroencephalographic (EEG) activity and hippocampal cytokines in the pentylenetetrazole (PTZ) model.

Pretreatment with CBD (60mg/kg) attenuated seizures induced by intraperitoneal, subcutaneous, and intravenous PTZ administration in mice. The effects were reversed by CB1, CB2, and TRPV1 selective antagonists (AM251, AM630, and SB366791, respectively). Additionally, CBD delayed seizure sensitization resulting from repeated PTZ administration (kindling). This cannabinoid also prevented PTZ-induced EEG activity and interleukin-6 increase in prefrontal cortex.

In conclusion, the robust anticonvulsant effects of CBD may result from multiple pharmacological mechanisms, including facilitation of endocannabinoid signaling and TRPV1 mechanisms. These findings advance our understanding on CBD inhibition of seizures, EEG activity, and cytokine actions, with potential implications for the development of new treatments for certain epileptic syndromes.”

https://www.ncbi.nlm.nih.gov/pubmed/28821005

http://www.epilepsybehavior.com/article/S1525-5050(17)30322-0/fulltext

The orphan receptor GPR55 is a novel cannabinoid receptor

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“Preparations of Cannabis sativa have been used for medicinal and recreational purposes for at least 4000 years and extracts of C. sativa contain over 60 different pharmacologically active components the most prominent being Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol

Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB1or CB2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55.

These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1and CB2 described here will permit delineation of its physiological function(s).”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

GPR55: A therapeutic target for Parkinson’s disease?

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“The GPR55 receptor is expressed abundantly in the brain, especially in the striatum, suggesting it might fulfill a role in motor function. Indeed, motor behavior is impaired in mice lacking GPR55, which also display dampened inflammatory responses.

Abnormal-cannabidiol (Abn-CBD), a synthetic cannabidiol (CBD) isomer, is a GPR55 agonist that may serve as a therapeutic agent in the treatment of inflammatory diseases.

In this study, we explored whether modulating GPR55 could also represent a therapeutic approach for the treatment of Parkinson’s disease (PD).

These results demonstrate for the first time that activation of GPR55 might be beneficial in combating PD.”

https://www.ncbi.nlm.nih.gov/pubmed/28807673

http://www.sciencedirect.com/science/article/pii/S0028390817303842

“The orphan receptor GPR55 is a novel cannabinoid receptor”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

Effects of Cannabidiol on Morphine Conditioned Place Preference in Mice.

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“This study sought to determine whether the cannabis constituent cannabidiol attenuates the development of morphine reward in the conditioned place preference paradigm.

Separate groups of mice received either saline or morphine in combination with one of four doses of cannabidiol using three sets of drug/no-drug conditioning trials. After drug-place conditioning, morphine mice displayed robust place preference that was attenuated by 10 mg/kg cannabidiol. Further, when administered alone, this dose of cannabidiol was void of rewarding and aversive properties.

The finding that cannabidiol blocks opioid reward suggests that this compound may be useful in addiction treatment settings.”

https://www.ncbi.nlm.nih.gov/pubmed/28793355

https://www.thieme-connect.de/DOI/DOI?10.1055/s-0043-117838

Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid.

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“The astrocytes have gained in recent decades an enormous interest as a potential target for neurotherapies, due to their essential and pleiotropic roles in brain physiology and pathology. Their precise regulation is still far from understood, although several candidate molecules/systems arise as promising targets for astrocyte-mediated neuroregulation and/or neuroprotection.

The cannabinoid system and its ligands have been shown to interact and affect activities of astrocytes. Cannabidiol (CBD) is the main non-psychotomimetic cannabinoid derived from Cannabis. CBD is devoid of direct CB1 and CB2 receptor activity, but exerts a number of important effects in the brain. Here, we attempt to sum up the current findings on the effects of CBD on astrocyte activity, and in this way on central nervous system (CNS) functions, across various tested models and neuropathologies.

The collected data shows that increased astrocyte activity is suppressed in the presence of CBD in models of ischemia, Alzheimer-like and Multiple-Sclerosis-like neurodegenerations, sciatic nerve injury, epilepsy, and schizophrenia. Moreover, CBD has been shown to decrease proinflammatory functions and signaling in astrocytes.”

https://www.ncbi.nlm.nih.gov/pubmed/28788104

http://www.mdpi.com/1422-0067/18/8/1669

Cannabinoid system of dorsomedial telencephalon modulates behavioral responses to noxious stimulation in the fish Leporinus macrocephalus.

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Physiology & Behavior

“Fish dorsomedial telencephalon has been considered a pallial region homologous to mammals amygdala, being considered a possible substrate for nociception modulation in this animal group. The present study aimed to evaluate the participation of the cannabinoid system of Dm telencephalon on nociception modulation in the fish Leporinus macrocephalus. We demonstrated that cannabidiol microinjection in Dm telecephalon inhibits the behavioral nociceptive response to the subcutaneous injection of 3% formaldehyde, and this antinociception is blocked by previous treatment with AM251 microinjection. Furthermore, AM251 microinjection in Dm prior to restraint stress also blockades the stress-induced antinociception. These results reinforce the hypothesis that this pallial telencephalic structure has a pivotal role in nociception modulation in fish.”

https://www.ncbi.nlm.nih.gov/pubmed/28754268

http://www.sciencedirect.com/science/article/pii/S0031938417302299?via%3Dihub

Could Cannabidiol be a Treatment Option for Intractable Childhood and Adolescent Epilepsy?

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 “Epilepsy is an important disease that affects brain function, particularly in those under 3 years old. Uncontrolled seizures can affect cognitive function and quality of life. For these reasons, many trials have been conducted to investigate treatments for pediatric epilepsy. Currently, many antiepileptic drugs are available for the treatment of epilepsy, but cases of intractable epilepsy continue to exist.

In the past, cannabis has been tested as a potential treatment of intractable epilepsy.

Since 2013, 10 epilepsy centers in America have conducted research regarding the efficacy of cannabis to treat epilepsy. Cannabis has many components, including cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). THC has psychoactive properties exerted through its binding of the cannabinoid receptor (CBR) whereas CBD is a CBR antagonist. The inhibition of epilepsy by CBD may therefore be caused by various mechanisms, although the detailed mechanisms of CBD actions have not yet been well defined. In most studies, trial doses of CBD were 2-5 mg/kg/day.

Several such studies have shown that CBD does have efficacy for treatment of epilepsy.

Reported adverse effects of CBD were mostly mild, including drowsiness, diarrhea, and decreased appetite. Severe adverse reactions requiring treatment, such as status epilepticus, have also been reported but it is not clear that this is related to CBD. Furthermore, many previous studies have been limited by an open-label or survey design. In future, double-blind, controlled trials are required and the use of CBD to treat other neurological problems should also be investigated.”  https://www.ncbi.nlm.nih.gov/pubmed/28775950

“Most studies suggest anticonvulsant effects of CBD, and consider most adverse effects to be mild. It must be borne in mind that CBD is still illegal in many contexts. However, it has the potential to treat various neurological problems, including epilepsy.” http://www.j-epilepsy.org/journal/view.php?doi=10.14581/jer.17003