Endocannabinoids activate transient receptor potential vanilloid 1 receptors to reduce hyperdopaminergia-related hyperactivity: therapeutic implications.

Posted on May 24, 2015 by David

“Knockout (KO) mice invalidated for the dopamine transporter (DAT) constitute a powerful animal model of neurobiological alterations associated with hyperdopaminergia relevant to schizophrenia and attention-deficit/hyperactivity disorder (ADHD).

CONCLUSIONS:

These data indicate a dysregulated striatal endocannabinoid neurotransmission associated with hyperdopaminergic state.

Restoring endocannabinoid homeostasis in active synapses might constitute an alternative therapeutic strategy for disorders associated with hyperdopaminergia.

In this process, TRPV1 receptors seem to play a key role and represent a novel promising pharmacological target.”

http://www.ncbi.nlm.nih.gov/pubmed/16199010

Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms.

Posted on May 14, 2015 by David

“Substance dependence and schizophrenia are both associated with dopaminergic dysfunction.

It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function.

These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/23820822

“There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels. Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence.” http://www.ncbi.nlm.nih.gov/pubmed/25873042

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

The relationship between cannabidiol and psychosis: A review.

Posted on May 9, 2015 by David

“Cannabis sativa is the most widely used illicit drug in the world…

THC is considered responsible for the main psychotropic effects of the drug, while CBD seems to antagonize these effects, particularly those that induce psychosis.

The effects of Cannabis seem to depend on several variables related to the type of plant, its strength, usage patterns, and intersubjective variations.

CBD could be used to treat several conditions, including psychosis, when the current treatment is associated with significant side effects.

…further research involving the possible antipsychotic effect and other potential positive effects of Cannabis are needed.”

http://www.ncbi.nlm.nih.gov/pubmed/25954940

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

Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine.

Posted on May 7, 2015 by David

“Drugs that facilitate dopaminergic neurotransmission such as amphetamine induce PPI disruption in human and rodents.

Clinical and neurobiological findings suggest that the endocannabinoid system and cannabinoids may be implicated in the pathophysiology and treatment of schizophrenia.

Cannabidiol (CBD), a non-psychotomimetic constituent of the Cannabis sativa plant, has also been reported to have potential as an antipsychotic.

Our aim was to investigate if CBD pretreatment was able to prevent PPI disruption induced by amphetamine…

Pretreatment with CBD attenuated the amphetamine-disruptive effects…

These results corroborate findings indicating that CBD induces antipsychotic-like effects.

In addition, they pointed to the nucleus accumbens as a possible site of these effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25943166

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

Cannabidiol in medicine: a review of its therapeutic potential in CNS disorders.

Posted on April 27, 2015 by David

“Cannabidiol (CBD) is the main non-psychotropic component of the glandular hairs of Cannabis sativa.

It displays a plethora of actions including anticonvulsive, sedative, hypnotic, antipsychotic, antiinflammatory and neuroprotective properties.

However, it is well established that CBD produces its biological effects without exerting significant intrinsic activity upon cannabinoid receptors.

For this reason, CBD lacks the unwanted psychotropic effects characteristic of marijuana derivatives, so representing one of the bioactive constituents of Cannabis sativa with the highest potential for therapeutic use.

The present review reports the pharmacological profile of CBD and summarizes results from preclinical and clinical studies utilizing CBD, alone or in combination with other phytocannabinoids, for the treatment of a number of CNS disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/18844286

The dopamine theory of addiction: 40 years of highs and lows.

Posted on April 16, 2015 by David

“For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum.

There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels.

Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.”

http://www.ncbi.nlm.nih.gov/pubmed/25873042

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

Drug repurposing and emerging adjunctive treatments for schizophrenia.

Posted on April 14, 2015 by David

“Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial.

Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs, as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones, glutamatergic and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoid modulator, represent promising agents in this field.”

http://www.ncbi.nlm.nih.gov/pubmed/25866122

Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

Posted on March 25, 2015 by David

“In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse.

This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/25801289

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

Association of single nucleotide polymorphisms in catechol-O-methyltransferase and serine-threonine protein kinase genes in the Pakistani schizophrenic population: a study with special emphasis on cannabis and smokeless tobacco.

Posted on March 25, 2015 by David

“Schizophrenia is a neuropsychiatric disorder in which abnormalities in the prefrontal cortex lead to impaired synthesis of dopamine. It is associated with hallucination, psychosis and hearing impairments. Many susceptible genes have been identified in schizophrenia such as catechol-O-methyltransferase (COMT) and serine/threonine kinase (AKT1).

Moreover, a study based on a single family showed COMT Met allele inheritance in schizophrenic offspring. This suggested that COMT allele alteration influences susceptibility to at least some forms of psychosis…

Interestingly, according to our socio-economic survey, COMT genotype has no association with cannabis but it is strongly associated with tobacco.”

http://www.ncbi.nlm.nih.gov/pubmed/25801838

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

For whom the endocannabinoid tolls: Modulation of innate immune function and implications for psychiatric disorders.

Posted on March 22, 2015 by David

“Over the past decade, there has been increasing evidence demonstrating that the endocannabinoid system can elicit potent modulatory effects on inflammatory processes, with clinical and preclinical evidence demonstrating beneficial effects on disease severity and symptoms in several inflammatory conditions.

This review examines the evidence supporting a modulatory effect of endocannabinoids on TLR-mediated immune responses both peripherally and centrally, and the implications for psychiatric disorders such as depression and schizophrenia.

CLASSES OF CANNABINOID-BASED PHARMACOLOGICAL AGENTS CITED IN THE REVIEW: Nonselective CB1/CB2 agonists: Δ9-THC, HU210, CP55940, WIN55,212-2 Selective CB2 agonists: JWH-015 FAAH inhibitors: URB597, AA-5HT MAGL/ABHD6 inhibitors: JZL184, MJN110, KML129, WWL70 Endocannabinoid reuptake inhibitors: UCM707, OMDM1/2, AM404.”

http://www.ncbi.nlm.nih.gov/pubmed/25794989