Cannabidiol monotherapy for treatment-resistant schizophrenia

Posted on June 21, 2016 by David

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“Cannabidiol (CBD), one of the major products of the marijuana plant, is devoid of marijuana’s typical psychological effects. In contrast, potential antipsychotic efficacy has been suggested based on preclinical and clinical data.

In this report, we further investigated the efficacy and safety of CBD monotherapy in three patients with treatment-resistant schizophrenia (TRS).

Efficacy, tolerability and side effects were assessed.

All patients tolerated CBD very well and no side effects were reported.

These preliminary data suggest that CBD monotherapy may not be effective for TRS.”

http://jop.sagepub.com/content/20/5/683.short

Hypothermia induced by delta9-tetrahydrocannabinol in rats with electrolytic lesions of preoptic region.

Posted on June 21, 2016 by David

“The preoptic region (POR) is a primary central site for thermoregulation. Bilateral lesions of POR disrupt thermoregulation, and in rats, produce a characteristic syndrome including hyperthermia.

delta9-Tetrahydrocannabinol (delta9-THC), a potent hypothermic agent, appears to mediate this effect via some central mechanism. The studies reported here suggest that delta9-THC induces hypothermia at a site other than POR.

These data demonstrate that delta9-THC is able to induce a hypothermic response in rats whose body temperatures were elevated by POR ablation. Although delta9-THC does not appear to act primarily at POR to induce hypothermia, it is evident than an intact POR plays a role in modifying the duration and magnitude of delta9-THC induced hypothermia.”

http://www.ncbi.nlm.nih.gov/pubmed/996043

Pharmacological hypothermia: a potential for future stroke therapy?

Posted on June 21, 2016 by David

“Mild physical hypothermia after stroke has been associated with positive outcomes.

Pharmacologically induced hypothermia has been explored as a possible treatment option following stroke in animal models.

Currently, there are eight classes of pharmacological agents/agonists with hypothermic effects affecting a multitude of systems including cannabinoid, opioid, transient receptor potential vanilloid 1 (TRPV1), neurotensin, thyroxine derivatives, dopamine, gas, and adenosine derivatives.

This review offers the opinion that these agents may be useful in combination therapies with physical hypothermia to achieve faster and more stable temperature control in hypothermia.”

http://www.ncbi.nlm.nih.gov/pubmed/27320243

Upregulation of the cannabinoid CB2 receptor in environmental and viral inflammation-driven rat models of Parkinson’s disease.

Posted on June 19, 2016 by David

“In recent years, it has become evident that Parkinson’s disease is associated with a self-sustaining cycle of neuroinflammation and neurodegeneration, with dying neurons activating microglia, which, once activated, can release several factors that kill further neurons.

One emerging pharmacological target that has the potential to break this cycle is the microglial CB₂ receptor which, when activated, can suppress microglial activity and reduce their neurotoxicity.

However, very little is known about CB₂ receptor expression in animal models of Parkinson’s disease which is essential for valid preclinical assessment of the anti-Parkinsonian efficacy of drugs targeting the CB₂ receptor.

Therefore, the aim of this study was to investigate and compare the changes that occur in CB₂ receptor expression in environmental and inflammation-driven models of Parkinson’s disease.

Thus, this study has shown that CB₂ receptor expression is dysregulated in animal models of Parkinson’s disease, and has also revealed significant differences in the level of dysregulation between the models themselves.

This study indicates that these models may be useful for further investigation of the CB₂ receptor as a target for anti-inflammatory disease modification in Parkinson’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/27317300

Modulation of cannabinoid signaling by hippocampal 5-HT4 serotonergic system in fear conditioning.

Posted on June 15, 2016 by David

“Behavioral studies have suggested a key role for the cannabinoid system in the modulation of conditioned fear memory. Likewise, much of the literature has revealed that the serotonergic system affects Pavlovian fear conditioning and extinction. A high level of functional overlap between the serotonin and cannabinoid systems has also been reported.

To clarify the interaction between the hippocampal serotonin (5-HT4) receptor and the cannabinoid CB1 receptor in the acquisition of fear memory, the effects of 5-HT4 agents, arachidonylcyclopropylamide (ACPA; CB1 receptor agonist), and the combined use of these drugs on fear learning were studied in a fear conditioning task in adult male NMRI mice.

Pre-training intraperitoneal administration of ACPA (0.1 mg/kg) decreased the percentage of freezing time in both context- and tone-dependent fear conditions, suggesting impairment of the acquisition of fear memory. Pre-training, intra-hippocampal (CA1) microinjection of RS67333, a 5-HT4 receptor agonist, at doses of 0.1 and 0.2 or 0.2 µg/mouse impaired contextual and tone fear memory, respectively. A subthreshold dose of RS67333 (0.005 µg/mouse) did not alter the ACPA response in either condition.

Moreover, intra-CA1 microinjection of RS23597 as a 5-HT4 receptor antagonist did not alter context-dependent fear memory acquisition, but it did impair tone-dependent fear memory acquisition. However, a subthreshold dose of the RS23597 (0.01 µg/mouse) potentiated ACPA-induced fear memory impairment in both conditions.

Therefore, we suggest that the blockade of hippocampal 5-HT4 serotonergic system modulates cannabinoid signaling induced by the activation of CB1 receptors in conditioned fear.”

http://www.ncbi.nlm.nih.gov/pubmed/27296273

Cannabidiol Modulates Fear Memory Formation through Interactions with Serotonergic Transmission in the Mesolimbic System.

Posted on June 15, 2016 by David

“Emerging evidence suggests that the largest phytochemical component of cannabis, cannabidiol (CBD), may possess pharmacotherapeutic properties in the treatment of neuropsychiatric disorders.

CBD has been reported to functionally interact with both the mesolimbic dopamine (DA) and serotonergic (5-HT) receptor systems.

Our findings demonstrate a novel NAcVTA circuit responsible for the behavioral and neuronal effects of CBD within the mesolimbic system via functional interactions with serotonergic 5-HT_1A receptor signalling.”

http://www.ncbi.nlm.nih.gov/pubmed/27296152

Treatment of Dravet Syndrome.

Posted on June 12, 2016 by David

“Dravet syndrome is among the most challenging electroclinical syndromes. There is a high likelihood of recurrent status epilepticus; seizures are medically refractory; and patients have multiple co-morbidities, including intellectual disability, behaviour and sleep problems, and crouch gait. Additionally, they are at significant risk of sudden unexplained death.

This review will focus predominantly on the prophylactic medical management of seizures, addressing both first-line therapies (valproate and clobazam) as well as second-line (stiripentol, topiramate, ketogenic diet) or later options (levetiracetam, bromides, vagus nerve stimulation). Sodium channel agents-including carbamazepine, oxcarbazepine, phenytoin and lamotrigine-should be avoided, as they typically exacerbate seizures.

Several agents in development may show promise, specifically fenfluramine and cannabidiol, but they need further evaluation in randomized, controlled trials.

In addition to prophylactic treatment, all patients need home-rescue medication and a status epilepticus protocol that can be carried out in their local hospital. Families must be counselled on non-pharmacologic strategies to reduce seizure risk, including avoidance of triggers that commonly induce seizures (including hyperthermia, flashing lights and patterns).

In addition to addressing seizures, holistic care for a patient with Dravet syndrome must involve a multidisciplinary team that includes specialists in physical, occupational and speech therapy, neuropsychology, social work and physical medicine.”

http://www.ncbi.nlm.nih.gov/pubmed/27264138

http://www.thctotalhealthcare.com/category/dravet-syndome/

Opioid and cannabinoid synergy in a mouse neuropathic pain model.

Posted on June 10, 2016 by David

“Clinical studies have reported that pan-cannabinoid receptor agonists may have efficacy in neuropathic pain states and that this might be enhanced by co-administration with opioids. While cannabinoid-opioid analgesic synergy has been demonstrated in animal models of acute pain, it has not been examined in neuropathic pain models. We examined the effect of combination treatment with cannabinoid and opioid receptor agonists on allodynia and side-effects in a nerve injury induced neuropathic pain model.

These findings indicate that combination administration of non-selective opioid and cannabinoid receptor agonists synergistically reduces nerve injury induced allodynia, while producing side-effects in an additive manner. This suggests that combination treatment has an improved anti-allodynic potency and therapeutic index in a neuropathic pain model.”

http://www.ncbi.nlm.nih.gov/pubmed/27278681

Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol.

Posted on June 10, 2016 by David

“Mutations in brain isoforms of voltage-gated sodium channels have been identified in patients with distinct epileptic phenotypes. Clinically, these patients often do not respond well to classic anti-epileptics and many remain refractory to treatment.

Exogenous as well as endogenous cannabinoids have been shown to target voltage-gated sodium channels and cannabidiol has recently received attention for its potential efficacy in the treatment of childhood epilepsies.

In this study, we further investigated the ability of cannabinoids to modulate sodium currents from wild-type and epilepsy-associated mutant voltage-gated sodium channels.

These findings suggest that cannabidiol could be exerting its anticonvulsant effects, at least in part, through its actions on voltage-gated sodium channels, and resurgent current may be a promising therapeutic target for the treatment of epilepsy syndromes.”

http://www.ncbi.nlm.nih.gov/pubmed/27267376

Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells.

Posted on June 4, 2016 by David

“Our previous studies showed that the non-psychoactive cannabinoid, cannabidiol (CBD), ameliorates the clinical symptoms in mouse myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis model of multiple sclerosis (MS) as well as decreases the memory MOG35-55-specific T cell (TMOG) proliferation and cytokine secretion including IL-17, a key autoimmune factor.

Microarray-based gene expression profiling demonstrated that CBD exerts its immunoregulatory effects in activated memory TMOG cells via (a) suppressing proinflammatory Th17-related transcription, (b) by promoting T cell exhaustion/tolerance, (c) enhancing IFN-dependent anti-proliferative program, (d) hampering antigen presentation, and (d) inducing antioxidant milieu resolving inflammation.

These findings put forward mechanism by which CBD exerts its anti-inflammatory effects as well as explain the beneficial role of CBD in pathological memory T cells and in autoimmune diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/27256343