Author Archives: David Worrell

Cannabinoid receptor activation in the basolateral amygdala blocks the effects of stress on the conditioning and extinction of inhibitory avoidance.

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“The endocannabinoid system has recently emerged as important in the regulation of extinction learning and in the regulation of the hypothalamic-pituitary-adrenal axis.

Here, we aimed to examine the involvement of the cannabinoid CB(1) receptor in the basolateral amygdala (BLA) in inhibitory avoidance (IA) conditioning and extinction and to test whether cannabinoid activation would reverse the effects of stress on these memory processes.

Together, our findings may support a wide therapeutic application for cannabinoids in the treatment of conditions associated with the inappropriate retention of aversive memories and stress-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/19741114

Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress.

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“Cannabinoids have recently emerged as a possible treatment of stress- and anxiety-related disorders such as post-traumatic stress disorder (PTSD).

Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of behavioral and neuroendocrine measures in a rat model of PTSD…

…cannabinoids could serve as a pharmacological treatment of stress- and trauma-related disorders.

…the results extend previous findings to another stress model and to a post-trauma treatment configuration that are more relevant to clinical context and add to the growing body of data pointing to a therapeutic potential of cannabinoids for treatment of PTSD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242307/

http://www.thctotalhealthcare.com/category/post-traumatic-stress-disorder-ptsd/

Cannabinoid receptor activation prevents the effects of chronic mild stress on emotional learning and LTP in a rat model of depression.

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“The endocannabinoid (eCB) system has recently emerged as a promising therapeutic target for the treatment of stress-related emotional disorders.

Recent data suggest that the eCB system could represent a new therapeutic target for the treatment of depression.

The findings suggest that enhancing cannabinoid signaling could represent a novel approach to the treatment of cognitive deficits that accompany stress-related depression.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924526/

http://www.thctotalhealthcare.com/category/depression-2/

Cannabinoid type-1 receptor signaling in central serotonergic neurons regulates anxiety-like behavior and sociability.

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“The endocannabinoid (eCB) system possesses neuromodulatory functions by influencing the release of various neurotransmitters, including γ-aminobutyric acid (GABA) and glutamate. A functional interaction between eCBs and the serotonergic system has already been suggested.

Previously, we showed that cannabinoid type-1 (CB1) receptor mRNA and protein are localized in serotonergic neurons of the raphe nuclei, implying that the eCB system can modulate serotonergic functions.

In order to substantiate the physiological role of the CB1 receptor in serotonergic neurons of the raphe nuclei, we generated serotonergic 5-hydroxytryptamine (5-HT) neuron-specific CB 1 receptor-deficient mice, using the Cre/loxP system with a tamoxifen-inducible Cre recombinase under the control of the regulatory sequences of the tryptophan hydroxylase 2 gene (TPH2-CreER (T2)), thus, restricting the recombination to 5-HT neurons of the central nervous system (CNS).

Applying several different behavioral paradigms, we revealed that mice lacking the CB1 receptor in serotonergic neurons are more anxious and less sociable than control littermates. Thus, we were able to show that functional CB1 receptor signaling in central serotonergic neurons modulates distinct behaviors in mice.”

http://www.ncbi.nlm.nih.gov/pubmed/26388750

In vitro and non-invasive in vivo effects of the cannabinoid-1 receptor agonist AM841 on gastrointestinal motor function in the rat.

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“Cannabinoids have been traditionally used for the treatment of gastrointestinal (GI) symptoms, but the associated central effects, through cannabinoid-1 receptors (CB1R), constitute an important drawback. Our aims were to characterize the effects of the recently developed highly potent long-acting megagonist AM841 on GI motor function and to determine its central effects in rats…

The CB1R megagonist AM841 may potently depress GI motor function in the absence of central effects. This effect may be mediated peripherally and may be useful in the treatment of GI motility disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26387676

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS).

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“Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic noncancer pain.

The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among subjects with chronic noncancer pain.

A standardized herbal cannabis product (12.5% THC) was dispensed to eligible subjects for a one-year period; controls were subjects with chronic pain from the same clinics who were not cannabis users.

The primary outcome consisted of serious adverse events (SAEs) and non-serious adverse events (AEs). Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver and endocrine function.

Secondary efficacy parameters included pain and other symptoms, mood, and quality of life.

Two hundred and sixteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 215 controls (chronic pain but no current cannabis use) from seven clinics across Canada. The median daily cannabis dose was 2.5g/d.

There was no difference in risk of SAEs between groups.

Medical cannabis users were at increased risk of non-serious AEs; most were mild to moderate. There were no differences in secondary safety assessments.

Quality-controlled herbal cannabis, when used by cannabis-experienced patients as part of a monitored treatment program over one year, appears to have a reasonable safety profile.

This study evaluated the safety of cannabis use by patients with chronic pain over one year. The study found that there was a higher rate of adverse events among cannabis users compared to controls but not for serious adverse events at an average dose of 2.5g herbal cannabis per day.”

http://www.ncbi.nlm.nih.gov/pubmed/26385201

http://www.thctotalhealthcare.com/category/pain-2/

Effect of combined doses of Δ9-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping.

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“Δ9-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea…

Combined subthreshold doses of THC  and CBDA reduced acute nausea.

Higher doses of THC or CBDA alone, as well as these combined doses also reduced acute nausea.

Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning.”

http://www.ncbi.nlm.nih.gov/pubmed/26381155

A Cannabinoid Receptor 2 Agonist Prevents Thrombin-Induced Blood-Brain Barrier Damage via the Inhibition of Microglial Activation and Matrix Metalloproteinase Expression in Rats.

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“Thrombin mediates the life-threatening cerebral edema and blood-brain barrier (BBB) damage that occurs after intracerebral hemorrhage (ICH).

We previously found that the selective cannabinoid receptor 2 (CB2R) agonist JWH-133 reduced brain edema and neurological deficits following germinal matrix hemorrhage (GMH).

We explored whether CB2R stimulation ameliorated thrombin-induced brain edema and BBB permeability as well as the possible molecular mechanism involved.

The results demonstrated that JWH-133 administration significantly decreased thrombin-induced brain edema and reduced the number of Iba-1-positive microglia…

We demonstrated that CB2R stimulation reduced thrombin-induced brain edema and alleviated BBB damage.”

http://www.ncbi.nlm.nih.gov/pubmed/26376816

Neural correlates of cannabidiol and Δ9-tetrahydrocannabinol interactions in mice: implications for medical cannabis.

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“It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Δ9-tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC.

The aim of this study is to investigate whether CBD modulates THC-induced functional effects and c-Fos expression in a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols.

These data re-affirm that CBD modulates the pharmacological actions of THC and provide information regarding brain regions involved in the interaction between CBD and THC.”

http://www.ncbi.nlm.nih.gov/pubmed/26377899

[Cannabis – therapy for the future?]

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“Despite all the progress achieved in the treatment of chronic gastrointestinal diseases, in some patients the treatment does not reach long-term optimum effectiveness. Therefore a number of patients have turned to complementary and alternative medicine (CAM).

Of the different types of CAM patients with GIT diseases tend to prefer in particular homeopathy, acupuncture and not least phytotherapy, where therapeutic use of cannabis may also be included.

The pathophysiological basis of therapeutic effect of curative cannabis has not been fully clarified so far.

Many scientists in many fields of medicine and pharmacology have been engaged in the study of effects of cannabinoids on the body since the beginning of the 20th century with the interest significantly increasing in the 1980s.

The discovery of CB receptors (1988) and endogenous molecules which activate these receptors (1992) led to the discovery of the endocannabinoid system.

Pharmacological modulation of the endogenous cannabinoid system offers new therapeutic possibilities of treatment of many illnesses and symptoms including the GIT disorders, including of nausea, vomiting, cachexia, IBS, Crohns disease and some other disorders.

Cannabinoids are attractive due to their therapeutic potential – they affect a lot of symptoms with minimum side effects.

Experience of patients with GIT disorders show that the use of cannabis is effective and helps in cases where the standard therapy fails.”

http://www.ncbi.nlm.nih.gov/pubmed/26375695