Probing the endocannabinoid system in healthy volunteers: Cannabidiol alters fronto-striatal resting-state connectivity.

European Neuropsychopharmacology Home

“Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are two substances from cannabis sativa that have been implicated in the treatment of mental and neurological disorders.

We concentrated on a previously validated neuroimaging phenotype, fronto-striatal connectivity across different striatal seeds, because of this loop’s relevance to executive functioning, decision making, salience generation and motivation and its link to various neuropsychiatric conditions. Therefore, we studied the effect of THC and CBD on fronto-striatal circuitry by a seed-voxel connectivity approach using seeds from the caudate and the putamen.

We conducted a cross-over pharmaco-fMRI study in 16 healthy male volunteers with placebo, 10 mg oral THC and 600 mg oral CBD. Resting state was measured in a 3 T scanner. CBD lead to an increase of fronto-striatal connectivity in comparison to placebo.

In contrast to our expectation that THC and CBD show opposing effects, THC versus placebo did not show any significant effects, probably due to insufficient concentration of THC during scanning.

The effect of CBD on enhancing fronto-striatal connectivity is of interest because it might be a neural correlate of its anti-psychotic effect in patients.”

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Neuronal and Molecular Effects of Cannabidiol on the Mesolimbic Dopamine System: Implications for Novel Schizophrenia Treatments.

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“Growing clinical and pre-clinical evidence points to a critical role for cannabidiol (CBD), the largest phytochemical component of cannabis, as a potential pharmacotherapy for various neuropsychiatric disorders.

In contrast to delta-9-tetrahydrocannabinol (THC), which is associated with acute and neurodevelopmental pro-psychotic side-effects, CBD possesses no known psychoactive or dependence-producing properties.

However, evidence has demonstrated that CBD strongly modulates the mesolimbic dopamine (DA) system and may possess promising anti-psychotic properties.

Despite the psychotropic differences between CBD and THC, little is known regarding their molecular and neuronal effects on the mesolimbic DA system, nor how these differential effects may relate to their potential pro vs. anti-psychotic properties.

This review summarizes clinical and pre-clinical evidence demonstrating CBD’s modulatory effects on DA activity states within the mesolimbic pathway, functional interactions with the serotonin 5-HT1A receptor system, and their downstream molecular signaling effects.

Together with clinical evidence showing that CBD may normalize affective and cognitive deficits associated with schizophrenia, CBD may represent a promising treatment for schizophrenia, acting through novel molecular and neuronal mesolimbic substrates.”

https://www.ncbi.nlm.nih.gov/pubmed/28185872

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Evaluation of Two Commercially Available Cannabidiol Formulations for Use in Electronic Cigarettes.

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“Since 24 states and the District of Columbia have legalized marijuana in some form, suppliers of legal marijuana have developed Cannabis sativa products for use in electronic cigarettes (e-cigarettes).

Personal battery powered vaporizers, or e-cigarettes, were developed to deliver a nicotine vapor such that smokers could simulate smoking tobacco without the inherent pathology of inhaled tobacco smoke. The liquid formulations used in these devices are comprised of an active ingredient such as nicotine mixed with vegetable glycerin (VG) and/or propylene glycol (PG) and flavorings.

A significant active ingredient of C. sativa, cannabidiol (CBD), has been purported to have anti-convulsant, anti-nociceptive, and anti-psychotic properties. These properties have potential medical therapies such as intervention of addictive behaviors, treatments for epilepsy, management of pain for cancer patients, and treatments for schizophrenia.

However, CBD extracted from C. sativa remains a DEA Schedule I drug since it has not been approved by the FDA for medical purposes.

Two commercially available e-cigarette liquid formulations reported to contain 3.3 mg/mL of CBD as the active ingredient were evaluated. These products are not regulated by the FDA in manufacturing or in labeling of the products and were found to contain 6.5 and 7.6 mg/mL of CBD in VG and PG with a variety of flavoring agents. Presently, while labeled as to content, the quality control of manufacturers and the relative safety of these products is uncertain.”

http://www.ncbi.nlm.nih.gov/pubmed/27621706

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Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

“Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily – largely within urban contexts – in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results.

An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases.

Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) – one of the numerous cannabinoid components found in cannabis – with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems.

The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users’ ‘self-medication’ efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. 

Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for – predominantly marginalized – crack-cocaine user populations.

Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use.

Given the high prevalence of this grave substance use problem in the Americas, opportunities for such research should urgently be created and facilitated there.” 

http://www.ncbi.nlm.nih.gov/pubmed/26500166

http://www.thctotalhealthcare.com/category/addiction/

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Medical Marijuana Is Safe for Children

“Numerous cases show clinical cannabis is effective on illnesses in children”

By  William Courtney, M.D. is CEO of Cannabis International.

“The courage and fortitude of parents who have chosen cannabis compounds to treat their children facing life-threatening illness have raised eyebrows. Some live in terror that their government will take their child away, since medical marijuana is only legal in some states. However, there are numerous cases demonstrating the benefits of clinical cannabis, which happen to threaten a very profitable healthcare industry that relies on conventional drugs, as well as political agendas.

The cannabinoid acids in cannabis have been found to have anti-proliferative, anti-neoplastic, anti-inflammatory, anti-epileptic, anti-ischemic, anti-diabetic, anti-psychotic, anti-nausea, anti-spasmodic, antibiotic, anti-anxiety, and anti-depressant functions. The anti-neoplastic action of cannabis—inhibiting development of malignant cells—was recognized in the 1970s and patented by the U.S. Department of Health and Human Services in 2003.

Out of 7,000 patients, my youngest, an 8-month-old, was diagnosed with a massive midbrain tumor. Pediatric oncologists recommended chemotherapy and radiation. Instead, the parents applied a cannabinoid concentrate to their son’s pacifier twice a day, which resulted in a significant reduction in the size of the tumor in 30 days. The response prevented a million-dollar chemo-radiation hospitalization. The child’s oncologist calls the infant a ‘miracle baby,’ but most medical experts would discount the case as anecdotal, unacceptable in a peer-reviewed journal. But the real peers are other parents reluctant to consent to the devastation of surgery, chemotherapy, and radiation—not those benefiting from the $2.6 trillion healthcare industry.

A 2-year-old spent a year in a pediatric oncology ward, endured 39 hours of brain surgery, received chemotherapy, a bone marrow transplant, and radiation under general anesthesia for 42 days, only to be discharged home on hospice and morphine. The child’s local pediatrician started to treat her with juiced raw cannabis leaf. Two years later, she is still alive, now free of cancer and scar tissue.

A 6-year-old patient with a severe, intractable form of childhood epilepsy, was tried on 11 anti-epileptics, including experimental European drugs. He was finally placed on a drug commonly used to prevent seizures, but continued having 300-400 seizures a day. An ointment produced from cannabis with an increased amount of cannabidiol, a compound patented by HHS, has reduced his seizures to one every 3-4 days.

Several years ago, I proposed that cannabis be recognized as an essential nutrient in the diet of individuals in their 30s and older. Children were excluded out of fear of backlash but it is now my incontrovertible opinion that the immune system of the 8-month-old would never have allowed the tumor to gain a foothold if supported with dietary cannabis, or Vitamin F.

We know Vitamin C deficiency results in scurvy and Vitamin D deficiency results in rickets. Vitamin F, the previous label for Omega-3 and -6 essential fatty acids, is an appropriate appellation for the cannabinoid acids found in cannabis. Vitamin F deficiency allows the cell proliferation found in tumors and cancer. Three studies of over 24,000 children have shown no adverse effects from use of cannabis in pregnancy.

There is no other area in medicine where the heavy hand of federal funding and political agenda compromise valid and reproducible findings to this extent. To advance disease prevention and benign therapy, we must re-examine our preconceptions.”

http://www.usnews.com/opinion/articles/2013/01/07/medical-marijuana-is-safe-for-children

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Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects.

“Over the last few years considerable attention has focused on cannabidiol (CBD), a major non-psychotropic constituent of Cannabis. In Part I of this review we present a condensed survey of the chemistry of CBD; in Part II, to be published later, we shall discuss the anti-convulsive, anti-anxiety, anti-psychotic, anti-nausea and anti-rheumatoid arthritic properties of CBD. CBD does not bind to the known cannabinoid receptors and its mechanism of action is yet unknown. In Part II we shall also present evidence that it is conceivable that, in part at least, its effects are due to its recently discovered inhibition of anandamide uptake and hydrolysis and to its anti-oxidative effect.”

http://www.ncbi.nlm.nih.gov/pubmed/12505688

http://www.scribd.com/doc/52920296/Cannabidiol-an-Overview-of-Some-Chemical-and-Pharmacological-Aspects-Part-I-Chemical-Aspects

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Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression.

“Pharmacological inhibition of beta-amyloid (Aβ) induced reactive gliosis may represent a novel rationale to develop drugs able to blunt neuronal damage and slow the course of Alzheimer’s disease (AD). Cannabidiol (CBD), the main non-psychotropic natural cannabinoid, exerts in vitro a combination of neuroprotective effects in different models of Aβ neurotoxicity. The present study, performed in a mouse model of AD-related neuroinflammation, was aimed at confirming in vivo the previously reported antiinflammatory properties of CBD.

Cannabidiol (CBD), the main non-psychotropic component of the glandular hairs of Cannabis sativa, exhibits a plethora of actions including anti-convulsive, sedative, hypnotic, anti-psychotic, anti-nausea, anti-inflammatory and anti-hyperalgesic properties. CBD has been proved to exert in vitro a combination of neuroprotective effects in Aβ-induced neurotoxicity, including anti-oxidant and anti-apoptotic effects, tau protein hyperphosphorylation inhibition through the Wnt pathway, and marked decrease of inducible nitric oxide synthase (iNOS) protein expression and nitrite production in Aβ-challenged differentiated rat neuronal cells.

In spite of the large amount of data describing the significant neuroprotective and anti-inflammatory properties of CBD in vitro, to date no evidence has been provided showing similar effects in vivo. To achieve this, the present study investigated the potential anti-inflammatory effect of CBD in a mouse model of AD-related neuroinflammation induced by the intrahippocampal injection of the human Aβ (1–42) fragment.

The results of the present study confirm in vivo anti-inflammatory actions of CBD, emphasizing the importance of this compound as a novel promising pharmacological tool capable of attenuating Aβ evoked neuroinflammatory responses.

 …on the basis of the present results, CBD, a drug well tolerated in humans, may be regarded as an attractive medical alternative for the treatment of AD, because of its lack of psychoactive and cognitive effects.”

Read more: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189818/

 

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