“There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects.
Tag Archives: Cannabinoids
Combined treatment with morphine and Δ9-tetrahydrocannibinol (THC) in rhesus monkeys: antinociceptive tolerance and withdrawal.
“Opioid receptor agonists are effective for treating pain; however, tolerance and dependence can develop with repeated treatment. Combining opioids with cannabinoids can enhance their analgesic potency…
These results demonstrate that antinociceptive tolerance is greater during treatment with the mixture, and although treatment conditions were sufficient for dependence to development on morphine, withdrawal was not markedly altered by concurrent treatment with THC.
Thus, THC can enhance some (antinociception, tolerance) but not all (dependence) effects of morphine.”
Role of cannabinoids in gastrointestinal mucosal defense and inflammation.
“Modulating the activity of the endocannabinoid system influences various gastrointestinal physiological and pathophysiological processes, and cannabinoid receptors as well as regulatory enzymes responsible for the synthesis or degradation of endocannabinoids represent potential targets to reduce the development of gastrointestinal mucosal lesions, hemorrhage and inflammation.
Direct activation of CB1 receptors by plant-derived, endogenous or synthetic cannabinoids effectively reduces both gastric acid secretion and gastric motor activity, and decreases the formation of gastric mucosal lesions induced by stress, pylorus ligation, nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol, partly by peripheral, partly by central mechanisms.
Similarly, indirect activation of cannabinoid receptors through elevation of endocannabinoid levels by globally acting or peripherally restricted inhibitors of their metabolizing enzymes (FAAH, MAGL) or by inhibitors of their cellular uptake reduced the gastric mucosal lesions induced by NSAIDs in a CB1 receptor-dependent fashion.
Dual inhibition of FAAH and cyclooxygenase induced protection against both NSAID-induced gastrointestinal damage and intestinal inflammation.
Moreover, in intestinal inflammation direct or indirect activation of CB1 and CB2 receptors exerts also multiple beneficial effects.
Namely, activation of both CB receptors was shown to ameliorate intestinal inflammation in various murine colitis models, to decrease visceral hypersensitivity and abdominal pain, as well as to reduce colitis-associated hypermotility and diarrhea.
In addition, CB1 receptors suppress secretory processes and also modulate intestinal epithelial barrier functions. Thus, experimental data suggest that the endocannabinoid system represents a promising target in the treatment of inflammatory bowel diseases, and this assumption is also confirmed by preliminary clinical studies.”
Cannabinoids: Medical implications.
“Herbal cannabis has been used for thousands of years for medical purposes.
With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored.
While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy.
While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards.
Where medical cannabis is legal, patients typically see a physician who “certifies” that a benefit may result.
Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis.
Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.
Key messages The medical disorders with the current best evidence that supports a benefit for cannabinoid use are the following: multiple sclerosis patient-reported symptoms of spasticity (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis central pain or painful spasms (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis bladder frequency (nabiximols), and chronic cancer pain/neuropathic pain (nabiximols and smoked THC).
Participating physicians should be knowledgeable about cannabinoids, closely look at the risk/benefit ratio, and consider certain important criteria in selecting a patient, such as: age, severity, and nature of the medical disorder, prior or current serious psychiatric or substance use disorder, failure of standard medical therapy as well as failure of an approved cannabinoid, serious underlying cardiac/pulmonary disease, agreement to follow-up visits, and acceptance of the detailed explanation of potential adverse risks.
The normal human endocannabinoid system is important in the understanding of such issues as normal physiology, cannabis use disorder, and the development of medications that may act as agonists or antagonists to CB1 and CB2.
By understanding the endocannabinoid system, it may be possible to enhance the beneficial effects of cannabinoid-related medication, while reducing the harmful effects.”
THC:CBD Observational Study Data: Evolution of Resistant MS Spasticity and Associated Symptoms.
“The prospective observational MObility ImproVEment (MOVE) 2 study is collecting real-life clinical outcomes data on patients with treatment-resistant multiple sclerosis (MS) spasticity treated with THC:CBD oromucosal spray in routine clinical practice. The MOVE 2 study has been ongoing in Italy, involving more than 30 MS centres across the country, since 2013.
RESULTS:
In the Italian cohort, THC:CBD oromucosal spray was added mainly to oral baclofen. Similar to MOVE 2-Germany, during 3 months’ observation, treatment discontinuations were limited and patients recorded meaningful improvements on the patient-based 0-10 numerical rating scale and physician-rated modified Ashworth scale at mean daily doses that were about one-third lower than those used in the RCT. Also, similar to MOVE 2-Germany, the proportion of patients reporting adverse events was about one-third of the rate recorded in the RCT.
CONCLUSIONS:
While MOVE 2-Italy continues, this interim analysis has enabled us to better define the place in therapy of THC:CBD oromucosal spray within the context of daily management of our patients with MS spasticity.”
THC:CBD in Daily Practice: Available Data from UK, Germany and Spain.
“A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported.
…no evidence of addiction, abuse or misuse.
The homogeneity between these observational studies supports the interest in THC:CBD oromucosal spray for management of MS spasticity in daily practice.”
http://www.ncbi.nlm.nih.gov/pubmed/26901342
http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/
Study the Effect of Endocannabinoid System on Rat Behavior in Elevated Plus-Maze.
“Previous studies have shown that cannabinoidergic system is involved in anxiety.
The aim of this study is to evaluate the effect of pharmacological stimulation or blocking of CB1 receptors and inhibition of endocannabinoid degradation in anxiety like behavior in elevated plus-maze (EPM) test in rat.
It is concluded that activation of cannabinoid receptor exert anxiolytic effect while blocking of cannabinoid receptor resulted in anxiety behavior. The locomotor activity was not significantly changed by cannabinoid system.
It is suggested that potentiation of cannabinoid system may be therapeutic strategy for the anxiety behavior.”
Plant-derived, synthetic and endogenous cannabinoids as neuroprotective agents. Non-psychoactive cannabinoids, ‘entourage’ compounds and inhibitors of N-acyl ethanolamine breakdown as therapeutic strategies to avoid pyschotropic effects.
“There is good evidence that plant-derived and synthetic cannabinoids possess neuroprotective properties.
These compounds, as a result of effects upon CB(1) cannabinoid receptors, reduce the release of glutamate, and in addition reduce the influx of calcium following NMDA receptor activation.
The major obstacle to the therapeutic utilization of such compounds are their psychotropic effects, which are also brought about by actions on CB(1) receptors. However, synthesis of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, which also have neuroprotective properties, are increased under conditions of severe inflammation and ischemia, raising the possibility that compounds that prevent their metabolism may be of therapeutic utility without having the drawback of producing psychotropic effects.
In this review, the evidence indicating neuroprotective actions of plant-derived, synthetic and endogenous cannabinoids is presented. In addition, the pharmacological properties of endogenous anandamide-related compounds that are not active upon cannabinoid receptors, but which are also produced during conditions of severe inflammation and ischemia and may contribute to a neuroprotective action are reviewed.”
Stimulation of cannabinoid CB1 receptors prevents nerve-mediated airway hyperreactivity in NGF-induced inflammation in mouse airways.
“In the present study, we tested the hypothesis that cannabinoids have both acute and chronic modulatory effects on nerve-mediated contractions in NGF-induced airway inflammation.
This study shows that stimulation of cannabinoid CB1 receptors modifies the increase of neuronal activity and density in NGF-induced airway inflammation and directly inhibits cholinergic contractions in the airways by a presynaptic mechanism.
These findings indicate a protective role of CB1 receptors in airway inflammation.”
Medical marijuana laws and adolescent marijuana use in the USA from 1991 to 2014: results from annual, repeated cross-sectional surveys.
“Our findings, consistent with previous evidence, suggest that passage of state medical marijuana laws does not increase adolescent use of marijuana.”
http://www.ncbi.nlm.nih.gov/pubmed/26303557
http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00217-5/fulltext