Tag Archives: cannabinoid

Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial.

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 “Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge. Nabiximols (Nabiximols is the U.S. Adopted Name [USAN] for Sativex [GW Pharma Ltd, Wiltshire, U.K.], which does not yet have an INN), a novel cannabinoid formulation, is undergoing investigation as add-on therapy…

This study supports the efficacy and safety of nabiximols at the 2 lower-dose levels and provides important dose information for future trials.

 PERSPECTIVE: Nabiximols, a novel cannabinoid formulation, may be a useful add-on analgesic for patients with opioid-refractory cancer pain. A randomized, double-blind, placebo-controlled, graded-dose study demonstrated efficacy and safety at low and medium doses.”

http://www.ncbi.nlm.nih.gov/pubmed/22483680

An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to Strong Opioid Analgesics.

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  “Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group.

OBJECTIVES:

This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer.

CONCLUSION:

This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/23141881

Enhanced endocannabinoid signaling elevates neuronal excitability in Fragile X syndrome

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 “Fragile X syndrome (FXS) results from deficiency of fragile X mental retardation protein (FMRP). FXS is the most common heritable form of mental retardation, and is associated with the occurrence of seizures. Factors responsible for initiating FXS-related hyperexcitability are poorly understood. Many protein-synthesis dependent functions of group I metabotropic glutamate receptors (Gp1 mGluRs) are exaggerated in FXS. Gp1 mGluR activation can mobilize endocannabinoids (eCBs) in the hippocampus and thereby increase excitability, but whether FMRP affects eCBs is unknown. We studied Fmr1 knockout (KO) mice lacking FMRP to test the hypothesis that eCB function is altered in FXS. Whole-cell, evoked inhibitory postsynaptic currents (eIPSCs), and field potentials were recorded in the CA1 region of acute hippocampal slices. Three eCB-mediated responses were examined: depolarization-induced suppression of inhibition (DSI), mGluR-initiated eCB short-term depression of eIPSCs (eCB-iSTD), and eCB-dependent inhibitory long-term depression (eCB-iLTD). Low concentrations of a Gp1 mGluR agonist produced larger eCB-mediated responses in Fmr1 KO mice than in WT mice, without affecting DSI. Western blots revealed that levels of mGluR1, mGluR5, or cannabinoid receptor (CB1R), were unchanged in Fmr1 KO animals, suggesting that the coupling between mGluR activation and eCB mobilization was enhanced by FMRP deletion. The increased susceptibility of Fmr1 KOslices to eCB-iLTD was physiologically relevant, since long-term potentiation of epsp-spike (E-S) coupling induced by the mGluR agonist was markedly larger in Fmr1 KO mice than in WT animals. Alterations in eCB signaling could contribute to the cognitive dysfunction associated with FXS…

The endocannabinoid system could represent another target for intervention in the treatment of FXS.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906112/

Cannabis Science And The Unconventional Foundation For Autism (UF4A) Partner To Advance Successful Cannabis-Based Autism Treatments

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  “Cannabis Science, Inc. (OTC Bulletin Board: CBIS), a pioneering US biotech company developing pharmaceutical cannabis products, is pleased to announce the partnership with The Unconventional Foundation for Autism (UF4A) to build on the Foundation’s success with its proprietary cannabinoid formulations for Autism treatment. The partnership will focus on advancing the medical cannabis treatments for Autism in conjunction with the successful cannabis treatments of Joey and 10 other families that are now being documented by The University of California Irvine Medical Center (UCI) for the Foundation.

These successful Autism treatments and pioneering efforts of Joey’s Mom, Mieko Hester Perez, can be fully reviewed here.

Mieko and the successful treatment of her son has garnered wide-spread media interest including television appearances and interviews with KABC 7 – Los Angeles & San Francisco, 20/20 ABC, Good Morning America, Fox Morning News, Fox News Rhode Island, CBS Early Show, KCAL 9 & CBS 2 Los Angeles, The Doctor’s TV Show, KABC 790 w/ Peter Tilden, Montel Williams, The Tom Joyner Show, The Kim Frasier Show w/ Dr. Lester Grinspoon, The Bill Press Show, NORML’s Podcast w/ Russ Belville, Thomasina Tafur radio show. Featured interviews: Autism Spectrum Magazine, Treating yourself Magazine, Huffington Post, Autism Spot, Celebstoner, disability scoop, Autism Support Network, Kush Magazine August 2010 Issue Cover, High Times Medical Marijuana Magazine Winter 2011 Issue, Treating yourself Magazine (Joey’s sibling interviewed Issue #23, Weed World UK Issue #89, Now Magazine UK Publications, Medical Cannabis Journal Issue, LA JEMM – Ethical Use of Medical Marijuana in the Treatment of Children with Autism, Orange County Register, California, The Revolution – Argentina publication. 2010 Recognized by the National Organization to Reform Marijauna Laws Woman’s Alliance as one of the woman making history in the medical marijuana movement.

Mieko Hester Perez, Founder and Executive Director of The Unconventional Foundation for Autism (UF4A) stated, “We believe that this new partnership with Cannabis Science will give us additional push and resources required to advance our Autism research. To date, we have already partnered with the University of California Irvine Medical Center to oversee our cannabis-based Autism research. Included in this group of advisors is the Dean of Medicine at UCI, and child psychiatrist Dr. Rebecca Hedrick M.D. Dr. Melamede of Cannabis Science will be an outstanding addition to the Board of the Foundation. His extensive knowledge of cannabinoid science should prove invaluable in our mission.”

As part of the new partnership, Dr. Robert Melamede, CEO of Cannabis Science, will be joining the board of UF4A as a scientific advisor. Dr. Melamede will work with UF4A to further assist in documenting the case studies and oversee the deployment of the Company’s proprietary cannabinoid treatments on Autism patients alongside UF4A and medical professionals. He will also work with UF4A’s legal advisors to progress the legalization of medical marijuana initiatives.

Dr. Robert Melamede Ph.D., Cannabis Science Inc., President & CEO, stated, “Cannabis Science’s partnership with UF4A is another instrumental step in reaching our long-term goal of FDA approval of the Company’s products. The successful results from the Autism patients treated as documented by UF4A are very encouraging and we’re excited to tap into UF4A’s proven track record; providing our scientific expertise to help develop more refined treatment plans with Cannabis Science’s formulations and extracts to achieve scientifically accepted patient outcomes. I’m also extremely excited to be working with the medical professionals at the University of California Irvine. This is a win-win for both our organizations in breaking new ground for medical cannabis treatments. Our partnership will enable both our Company and UF4A to expound upon studies and anecdotal evidence obtained by UF4A in order to catalogue verified case studies and solid science behind the treatment plans. This evidentiary step will help the UF4A and Cannabis Science partnership to move towards formal FDA testing to officially approve UF4A’s successful treatments of Autism using medical cannabinoid extracts and formulations under the direction of physicians. ”

UF4A Case Studies

Mieko Hester-Perez and her son “Joey” have inspired many additional parents with autistic children to step forward. Studies are underway with these children with oversight from Child & Adolescent Psychiatrist Dr. Rebecca M. Hedrick, M.D.

Dr. Hedrick is a child and adolescent emergency attending physician and covers the consult liaison service at UCI Medical. She runs a child and adolescent outpatient psychotherapy and medication management program. She also works with the Regional Center of Orange County in the treatment of individuals with developmental disabilities.”

 http://www.medicalnewstoday.com/releases/219569.php

Consequences of Cannabinoid and Monoaminergic System Disruption in a Mouse Model of Autism Spectrum Disorders

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“Autism is a behaviorally defined neurodevelopmental disorder characterized by impairments in social interaction and communication and repetitive/stereotyped behaviors . The cause of autism is not completely understood and there is no effective cure. However, genetic and environmental factors and the interaction between genes and environment are known to play a role in Autism Spectrum Disorders (ASDs)…

Our data provides a basis for further studies in evaluating the role of the cannabinoid and monoaminergic systems in the etiology of ASDs.

It is tempting to suggest the evaluation of Δ9-THC or other cannabinoids with reduced psychoactivity in irritability, tantrums and self-injurious behavior associated with autistic individuals.

 The rationale for this novel hypothesis arises from the discovery that the endocannabinoid system is one of the most abundant physiological control systems in animals and humans.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137184/

Cannabinoid mechanisms of pain suppression.

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Abstract

“A large body of literature indicates that cannabinoids suppress behavioral responses to acute and persistent noxious stimulation in animals. This review examines neuroanatomical, behavioral, and neurophysiological evidence supporting a role for cannabinoids in suppressing pain at spinal, supraspinal, and peripheral levels. Localization studies employing receptor binding and quantitative autoradiography, immunocytochemistry, and in situ hybridization are reviewed to examine the distribution of cannabinoid receptors at these levels and provide a neuroanatomical framework with which to understand the roles of endogenous cannabinoids in sensory processing. Pharmacological and transgenic approaches that have been used to study cannabinoid antinociceptive mechanisms are described. These studies provide insight into the functional roles of cannabinoid CB1 (CB1R) and CB2 (CB2R) receptor subtypes in cannabinoid antinociceptive mechanisms, as revealed in animal models of acute and persistent pain. The role of endocannabinoids and related fatty acid amides that are implicated in endogenous mechanisms for pain suppression are discussed. Human studies evaluating therapeutic potential of cannabinoid pharmacotherapies in experimental and clinical pain syndromes are evaluated. The potential of exploiting cannabinoid antinociceptive mechanisms in novel pharmacotherapies for pain is discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/16596786

Cannabinoids and pain.

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Abstract

“Recent advances have dramatically increased our understanding of cannabinoid pharmacology: the psychoactive constituents of Cannabis sativa have been isolated, synthetic cannabinoids described and an endocannabinoid system identified, together with its component receptors, ligands and their biochemistry. Strong laboratory evidence now underwrites anecdotal claims of cannabinoid analgesia in inflammatory and neuropathic pain. Sites of analgesic action have been identified in brain, spinal cord and the periphery, with the latter two presenting attractive targets for divorcing the analgesic and psychotrophic effects of cannabinoids. Clinical trials are now required, but are hindered by a paucity of cannabinoids of suitable bioavailability and therapeutic ratio.”

http://www.ncbi.nlm.nih.gov/pubmed/11575713

[The pharmacology of cannabinoid derivatives: are there applications to treatment of pain?].

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“OBJECTIVE:

To present the cannabinoid system together with recent findings on the pharmacology of these compounds in the treatment of pain.

DATA SOURCES:

Search through Medline database of articles published in French and English since 1966. Also use of other publications such as books on cannabis.

DATA SYNTHESIS:

Recent advances have dramatically increased our understanding of cannabinoid pharmacology. The psychoactive constituents of Cannabis sativa have been isolated, synthetic cannabinoids described and an endocannabinoid system identified, together with its component receptors and ligands. Strong laboratory evidence now underwrites anecdotal claims of cannabinoid analgesia in inflammatory and neuropathic pain. Sites of analgesic action have been identified in brain, spinal cord and the periphery, with the latter two presenting attractive targets for divorcing the analgesic and psychotrophic effects of cannabinoids. Clinical trials are now required, but are hindered by a paucity of cannabinoids of suitable bioavailability and therapeutic ratio.

CONCLUSION:

The cannabinoid system is a major target in the treatment of pain and its therapeutic potential should be assessed in the near future by the performance of new clinical trials.”

http://www.ncbi.nlm.nih.gov/pubmed/12134594

Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain.

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Abstract

“OBJECTIVE:

To review the literature concerning the physiology of the endocannabinoid system, current drug development of cannabinoid agonists, and current clinical research on the use of cannabinoid agonists for analgesia.

DATA SOURCES:

Articles were identified through a search of MEDLINE (1966-August 2005) using the key words cannabis, cannabinoid, cannabi*, cannabidiol, nabilone, THC, pain, and analgesia. No search limits were included. Additional references were located through review of the bibliographies of the articles identified.

STUDY SELECTION AND DATA EXTRACTION:

Studies of cannabinoid agonists for treatment of pain were selected and were not limited by pain type or etiology. Studies or reviews using animal models of pain were also included. Articles that related to the physiology and pharmacology of the endocannabinoid system were evaluated.

DATA SYNTHESIS:

The discovery of cannabinoid receptors and endogenous ligands for these receptors has led to increased drug development of cannabinoid agonists. New cannabimimetic agents have been associated with fewer systemic adverse effects than delta-9-tetrahydrocannabinol, including recent development of cannabis medicinal extracts for sublingual use (approved in Canada), and have had promising results for analgesia in initial human trials. Several synthetic cannabinoids have also been studied in humans, including 2 cannabinoid agonists available on the international market.

CONCLUSIONS:

Cannabinoids provide a potential approach to pain management with a novel therapeutic target and mechanism. Chronic pain often requires a polypharmaceutical approach to management, and cannabinoids are a potential addition to the arsenal of treatment options.”

http://www.ncbi.nlm.nih.gov/pubmed/16449552

Targeting cannabinoid agonists for inflammatory and neuropathic pain.

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Abstract

“The cannabinoid receptors CB(1) and CB(2) are class A G-protein-coupled receptors. It is well known that cannabinoid receptor agonists produce relief of pain in a variety of animal models by interacting with cannabinoid receptors. CB(1) receptors are located centrally and peripherally, whereas CB(2) receptors are expressed primarily on immune cells and tissues. A large body of preclinical data supports the hypothesis that either CB(2)-selective agonists or CB(1) agonists acting at peripheral sites, or with limited CNS exposure, will inhibit pain and neuroinflammation without side effects within the CNS. There has been a growing interest in developing cannabinoid agonists. Many new cannabinoid ligands have been synthesized and studied covering a wide variety of novel structural scaffolds. This review focuses on the present development of cannabinoid agonists with an emphasis on selective CB(2) agonists and peripherally restricted CB(1) or CB(1)/CB(2) dual agonists for treatment of inflammatory and neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/17594182