:
“Spasticity in chronic spinal cord injury is a condition that can have negative repercussions on the patient’s quality of life. Its treatment is complex and sometimes the outcome is insufficient.
Cannabinoids have recently been used in multiple sclerosis to successfully treat spasticity that is refractory to other therapies.
Category Archives: THC (Delta-9-Tetrahydrocannabinol)
Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as Adjunctive Therapy in Advanced Cancer Patients With Chronic Uncontrolled Pain.
“Prior phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancer patients with uncontrolled pain. To assess adjunctive nabiximols (Sativex®), an extract of Cannabis sativa containing two potentially therapeutic cannabinoids (Δ9-tetrahydrocannabinol and cannabidiol, in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy. Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at week 3 and on all three at week 5. The safety profile of nabiximols was consistent with earlier studies.
Although not superior to placebo on the primary efficacy endpoint, nabiximols had benefits on multiple secondary endpoints, particularly in US patients.
Nabiximols might have utility in patients with advanced cancer who receive a lower opioid dose, such as individuals with early intolerance to opioid therapy.”
https://www.ncbi.nlm.nih.gov/pubmed/28923526 http://www.jpsmjournal.com/article/S0885-3924(17)30465-7/fulltext]]>Maternal and infant outcomes following third trimester exposure to marijuana in opioid dependent pregnant women maintained on buprenorphine.
“Analyses failed to support any significant relationship between marijuana use in the third trimester and a variety of maternal and infant outcomes. Preliminary results indicate that marijuana exposure in the third trimester does not complicate the pregnancy or the delivery process.” https://www.ncbi.nlm.nih.gov/pubmed/28917206 http://www.drugandalcoholdependence.com/article/S0376-8716(17)30443-X/fulltext]]>
Effects of coadministration of low dose cannabinoid type 2 receptor agonist and morphine on vanilloid receptor 1 expression in a rat model of cancer pain.
“Morphine is widely used as an analgesic to treat moderate to severe pain, but chronic morphine use is associated with development of tolerance and dependence, which limits its analgesic efficacy. Our previous research has showed that nonanalgetic dose of a cannabinoid type 2 (CB2) receptor agonist reduced morphine tolerance in cancer pain. A previous study showed the colocalization of CB2 and transient receptor potential vanilloid 1 (TRPV1) in human and rat dorsal root ganglia (DRG) sensory neurons. Whether coadministration of a CB2 receptor agonist and morphine could reduce TRPV1 expression in morphine‑induced antinociception and tolerance in cancer pain is unclear. Therefore, we investigated the effects of coadministration of a CB2 receptor agonist AM1241 and morphine on TRPV1 expression and tolerance in cancer pain. Coadministration of AM1241 and morphine for 8 days significantly reduced morphine tolerance, as assessed by measuring paw withdrawal latency to a radiant heat stimulation, in Walker 256 tumor‑bearing rats. Repeated morphine treatment for a period of 8 days induced upregulation of the TRPV1 protein expression levels in the DRG in the tumor‑bearing rats, although no change in mRNA expression. Pretreatment with AM1241 reduced this morphine‑induced upregulation of TRPV1 and the effect was reversed by the CB2 receptor antagonist AM630. Our findings suggest that coadministration of a CB2 receptor agonist AM1241 and morphine reduced morphine tolerance possibly through regulation of TRPV1 protein expression in the DRG in cancer pain.”
https://www.ncbi.nlm.nih.gov/pubmed/28901432
https://www.spandidos-publications.com/10.3892/mmr.2017.7479
11-nor-9-carboxy-Δ9-tetrahydrocannabinol glucuronide exhibits acyl-migration isomers.
“11-nor-Δ9-Tetrahydrocannabinol-9-carboxylic acid glucuronide (THCCOOH-glucuronide) is an 1-β-O-acyl glucuronide which degrades not only to 11-nor-9-carboxy-Δ9-THC (THCCOOH) but, additionally, to an isomer with a currently unknown structure. The present study was carried out to examine whether acyl glucuronide isomers are formed by acyl migration and if they are involved in formation of this isomer. THCCOOH-glucuronide was incubated in phosphate buffer (pH 7.4, 37°C, 7days) and a variety of glucuronide cleavage procedures were performed. Samples of the incubation mixture and of different biological specimens from cannabis users were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). A total of six chromatographically separated isomeric acyl glucuronides were detected during incubation of THCCOOH-glucuronide reference substance. In biological specimens of cannabis users, two additional isomers were found. However, the main glucuronide present in human specimens was different from that of a commercially available reference substance. Both, the commercial and the authentic glucuronide were cleaved by β-glucuronidases, the other formed isomers by alkaline hydrolysis only. Mass spectrometric investigations (i.e. product ion, precursor ion and neutral loss scans) confirmed identity. The THCCOOH isomer was detected in all authentic samples, but not in those after buffer incubation. By analyzing THCCOOH-glucuronide in authentic samples, it has to be taken into account that the authentic glucuronide is different from that of the commercial reference standard. THCCOOH-glucuronide undergoes acyl migration and some isomers occur to minor extents in biological specimens. Acyl migration does not lead to the formation of the THCCOOH isomer.” https://www.ncbi.nlm.nih.gov/pubmed/28892757 http://www.sciencedirect.com/science/article/pii/S0731708517317090?via%3Dihub]]>
Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration.
“Nowadays, therapeutic indications for cannabinoids, specifically Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is its composition of materials approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans. In order to evaluate the pharmacokinetic profile of the THC-CBD-piperine-PNL formulation, a two-way crossover, single administration clinical study was conducted. The trial comprised of 9 healthy volunteers under fasted conditions. Each subject received a THC-CBD (1:1, 10mg) piperine (20mg)-PNL filled capsule and an equivalent dose of the oromucosal spray Sativex® with a washout period in between treatments. Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. These findings demonstrate the potential this formulation has in serving as a standardized oral cannabinoid formulation. Moreover, the concept of improving oral bioavailability described here, can pave the way for other potential lipophilic active compounds requiring enhancement of their oral bioavailability.” https://www.ncbi.nlm.nih.gov/pubmed/28890215 http://www.sciencedirect.com/science/article/pii/S016836591730843X]]>
Distinct roles of neuronal and microglial CB2 cannabinoid receptors in the mouse hippocampus.
“The effects of cannabinoids are primarily mediated by type-1 cannabinoid receptors in the brain and type-2 cannabinoid receptors (CB2Rs) in the peripheral immune system. However, recent evidence demonstrates that CB2Rs are also expressed in the brain and implicated in neuropsychiatric effects. Diverse types of cells in various regions in the brain express CB2Rs but the cellular loci of CB2Rs that induce specific behavioral effects have not been determined. To manipulate CB2R expression in specific types of cells in the dorsal hippocampus of adult mice, we used Cre-dependent overexpression and CRISPR-Cas9 genome editing techniques in combination with adeno-associated viruses and transgenic mice. Elevation and disruption of CB2R expression in microglia in the CA1 area increased and decreased, respectively, contextual fear memory. In CA1 pyramidal neurons, disruption of CB2R expression enhanced spatial working memory, whereas their overexpression reduced anxiety levels assessed as an increase in the exploration time in the central area of open field. Interneuronal CB2Rs were not involved in the modulation of cognitive or emotional behaviors tested in this study. The targeted manipulation of CB2R expression in pyramidal neurons and microglia suggests that CB2Rs in different types of cells in the mature hippocampus play distinct roles in the regulation of memory and anxiety.” https://www.ncbi.nlm.nih.gov/pubmed/28888955 http://www.sciencedirect.com/science/article/pii/S0306452217306292]]>
Treatment of human spasticity with delta 9-tetrahydrocannabinol.
“Spasticity is a common neurologic condition in patients with multiple sclerosis, stroke, cerebral palsy or an injured spinal cord. Animal studies suggest that THC has an inhibitory effect on polysynaptic reflexes.
Some spastic patients claim improvement after inhaling cannabis. We tested muscle tone, reflexes, strength and performed EMGs before and after double-blinded oral administration of either 10 or 5 mg THC or placebo.
10 mg THC significantly reduced spasticity by clinical measurement (P less than 0.01).
Responses varied, but benefit was seen in three of three patients with “tonic spasms.””
“Cannabis and its psychoactive constituent Δ9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain however, this is hampered by their side-effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side-effects.
We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. Acute systemic administration of THC dose-dependently reduced CCI-induced mechanical and cold allodynia, but also produced motor incoordination, catalepsy and sedation. CBD produced a lesser dose-dependent reduction in allodynia, but did not produce the