Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Ligands of the CB2 cannabinoid receptors augment activity of the conventional antidepressant drugs in the behavioural tests in mice.

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Behavioural Brain Research“Although a lot of information can be found on the specific dual role of the endocannabinoid system in the emotional-related responses, little is known whether stimulation or inhibition of the CB receptors may affect the activity of the frequently prescribed antidepressant drugs.

Our interests have been particularly focused on the potential influence of the CB2 receptors, as the ones whose central effects are relatively poorly documented when compared to the central effects of the CB1 receptors. Therefore, we evaluated the potential interaction between the CB2 receptor ligands (i.e., JWH133 – CB2 receptor agonist and AM630 – CB2 receptor inverse agonist) and several common antidepressant drugs that influence the monoaminergic system (i.e., imipramine, escitalopram, reboxetine).

Summarizing, the results of the present study revealed that both activation and inhibition of the CB2 receptor function have a potential to strengthen the antidepressant activity of drugs targeting the monoaminergic system. Most probably, the described interaction has a pharmacodynamic background.”

https://www.ncbi.nlm.nih.gov/pubmed/31626848

“Interplay between CB2 receptor ligands and antidepressants is pharmacodynamic in nature.”

https://www.sciencedirect.com/science/article/pii/S0166432819311891?via%3Dihub

Neuropeptide Y and cannabinoids interaction in the amygdala after exposure to shock and reminders model of PTSD.

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Neuropharmacology“Modulation of cannabinoid and neuropeptide Y (NPY) receptors may offer therapeutic benefits for post-traumatic stress disorder (PTSD).

In this study, we aimed to investigate the functional interaction between these systems in the basolateral amygdala (BLA) in a rat model of PTSD.

The findings suggest that the functional interaction between the eCB and NPY1 systems is complex and provide a rationale for exploring novel therapeutic strategies that target the cannabinoid and NPY systems for stress-related diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/31622603

https://www.sciencedirect.com/science/article/pii/S0028390819303661?via%3Dihub

‘Standard THC Units’: a proposal to standardise dose across all cannabis products and methods of administration.

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Publication cover image“Cannabis products are becoming increasingly diverse, and they vary considerably in concentrations of ∆9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). Higher doses of THC can increase the risk of harm from cannabis, while CBD may partially offset some of these effects. Lower Risk Cannabis Use Guidelines currently lack recommendations based on quantity of use, and could be improved by implementing standard units. However, there is currently no consensus on how units should be measured or standardised across different cannabis products or methods of administration.

ARGUMENT:

Existing proposals for standard cannabis units have been based on specific methods of administration (e.g. joints) and these may not capture other methods including pipes, bongs, blunts, dabbing, vaporizers, vape pens, edibles and liquids. Other proposals (e.g. grams of cannabis) cannot account for heterogeneity in THC concentrations across different cannabis products. Similar to alcohol units, we argue that standard cannabis units should reflect the quantity of active pharmacological constituents (dose of THC). On the basis of experimental and ecological data, public health considerations, and existing policy we propose that a ‘Standard THC Unit’ should be fixed at 5 milligrams of THC for all cannabis products and methods of administration. If supported by sufficient evidence in future, consumption of Standard CBD Units might offer an additional strategy for harm reduction.

CONCLUSIONS:

Standard THC Units can potentially be applied across all cannabis products and methods of administration to guide consumers and promote safer patterns of use.”

https://www.ncbi.nlm.nih.gov/pubmed/31606008

https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14842

Cellular Distribution of Canonical and Putative Cannabinoid Receptors in Canine Cervical Dorsal Root Ganglia.

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Image result for frontiers in veterinary science“Growing evidence indicates cannabinoid receptors as potential therapeutic targets for chronic pain.

Consequently, there is an increasing interest in developing cannabinoid receptor agonists for treating human and veterinary pain.

The present study may represent a morphological substrate to consider in order to develop therapeutic strategies against chronic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/31608295

“The anti-nociceptive potential of the endocannabinoid system has prompted the development of therapeutic cannabinoid receptors agonists or medical marjiuana to be used in pets in order to treat chronic pain.”

https://www.frontiersin.org/articles/10.3389/fvets.2019.00313/full

CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment.

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Publication cover image

“Periodontitis is an inflammatory immune disease that causes periodontal tissue loss. Inflammatory immunity and bone metabolism are closely related to periodontitis.

The cannabinoid receptor I (CB1) is an important constituent of the endocannabinoid system and participates in bone metabolism and inflammation tissue healing.

It is unclear whether CB1 affects the mesenchymal stem cell (MSC) function involved in periodontal tissue regeneration.

In this study, we revealed the role and mechanism of CB1 in the osteo/dentinogenic differentiation of periodontal ligament stem cells (PDLSCs) in an inflammatory environment.

CONCLUSIONS:

CB1 was able to enhance the osteo/dentinogenic differentiation ability of PDLSCs via p38 MAPK and JNK signalling in an inflammatory environment, which might be a potential target for periodontitis treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/31599069

“In conclusion, our findings revealed that CB1 could activate the osteo/dentinogenic differentiation potential of PDLSCs under inflammatory conditions. Our results clarified the potential role and mechanism of CB1 in PDLSCs under inflammatory conditions and provide candidate targets for enhancing MSC function and the treatment of periodontitis.”

https://onlinelibrary.wiley.com/doi/full/10.1111/cpr.12691

The Effects of Dosage-Controlled Cannabis Capsules on Cancer-Related Cachexia and Anorexia Syndrome in Advanced Cancer Patients: Pilot Study.

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Image result for integrative cancer therapies“Cancer-related cachexia and anorexia syndrome (CACS) is a common phenomenon in cancer patients. Cannabis has been suggested to stimulate appetite but research on this issue has yielded mixed results. The current study aimed to evaluate the effect of dosage-controlled cannabis capsules on CACS in advanced cancer patients.

Methods: The cannabis capsules used in this study contained two fractions of oil-based compounds. The planned treatment was 2 × 10 mg per 24 hours for six months of tetrahydrocannabinol (THC) 9.5 mg and cannabidiol (CBD) 0.5 mg. If patients suffered from side effects, dosage was reduced to 5 mg × 2 per day (THC 4.75 mg, CBD 0.25 mg). Participants were weighed on every physician visit. The primary objective of the study was a weight gain of ≥10% from baseline.

Results: Of 24 patients who signed the consent form, 17 started the cannabis capsules treatment, but only 11 received the capsules for more than two weeks. Three of six patients who completed the study period met the primary end-point. The remaining three patients had stable weights. In quality of life quaternaries, patients reported less appetite loss after the cannabis treatment (p=0.05). Tumor necrosis factor-α (TNF-α) levels decreased after the cannabis treatment but without statistical significance. According to patients’ self-reports, improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated.

Conclusions: Despite various limitations, this preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) patients with doses of 5mgx1 or 5mgx2 capsules daily, without significant side effects. The results justify a larger study with dosage-controlled cannabis capsules in CACS.”

https://www.ncbi.nlm.nih.gov/pubmed/31595793

“The primary objective of the study was a weight gain of ≥10% from baseline. Despite various limitations, the current preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) of the patients with doses of 5 mg × 1 or 5 mg × 2 capsules daily, without significant side effects.”

https://journals.sagepub.com/doi/10.1177/1534735419881498

Cannabinoid Receptor Type 1 and Its Role as an Analgesic: An Opioid Alternative?

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 Publication Cover“Understanding how the body regulates pain is fundamental to develop rational strategies to combat the growing prevalence of chronic pain states, opioid dependency, and the increased financial burden to the medical care system.

Pain is the most prominent reason why Americans seek medical attention and extensive literature has identified the importance of the endocannabinoid pathway in controlling pain. Modulation of the endocannabinoid system offers new therapeutic opportunities for the selective control of excessive neuronal activity in several pain conditions (acute, inflammatory, chronic, and neuropathic).

Cannabinoids have a long history of medicinal use and their analgesic properties are well documented; however, there are major impediments to understanding cannabinoid pain modulation.

One major issue is the presence of psychotropic side effects associated with D9-tetrahydrocannabinol (THC) or synthetic derivatives, which puts an emphatic brake on their use. This dose-limiting effect prevents the appropriate degree of analgesia .

Animal studies have shown that the psychotropic effects are mediated via brain cannabinoid type 1 (CB1) receptors, while analgesic activity in chronic pain states may be mediated via CB1R action in the spinal cord, brainstem, peripheral sensory neurons, or immune cells.

The development of appropriate therapies is incumbent on our understanding of the role of peripheral versus central endocannabinoid-driven analgesia. Recent physiological, pharmacological, and anatomical studies provide evidence that one of the main roles of the endocannabinoid system is the regulation of gamma-aminobutyric acid (GABA) and/or glutamate release.

This article will review this evidence in the context of its implications for pain. We first provide a brief overview of CB1R’s role in the regulation of nociception, followed by a review of the evidence that the peripheral endocannabinoid system modulates nociception.

We then look in detail at regulation of central-mediated analgesia, followed up with evidence that cannabinoid mediated modulation of pain involves modulation of GABAergic and glutamatergic neurotransmission in key brain regions. Finally, we discuss cannabinoid action on non-neuronal cells in the context of inflammation and direct modulation of neurons.

This work stands to reveal long-standing controversies in the cannabinoid analgesia area that have had an impact on failed clinical trials and implementation of therapeutics targeting this system.”

https://www.ncbi.nlm.nih.gov/pubmed/31596190

https://www.tandfonline.com/doi/abs/10.1080/15504263.2019.1668100?journalCode=wjdd20

Δ9-Tetrahydrocannabinol Derivative-Loaded Nanoformulation Lowers Intraocular Pressure in Normotensive Rabbits.

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“Δ9-Tetrahydrocannabinol-valine-hemisuccinate, a hydrophilic prodrug of Δ9-tetrahydrocannabinol, synthesized with the aim of improving the ocular bioavailability of the parent molecule, was investigated in a lipid-based nanoparticle dosage form for ocular delivery.

RESULTS:

A peak intraocular pressure (IOP) drop of 30% from baseline was observed in rabbits treated with SLNs loaded with Δ9-tetrahydrocannabinol-valine-hemisuccinate at 90 minutes. Treated eyes of rabbits receiving Δ9-tetrahydrocannabinol-valine-hemisuccinate SLNs had significantly lower IOP than untreated eyes until 360 minutes, whereas the group receiving the emulsion formulation showed a drop in IOP until 90 minutes only. In comparison to marketed pilocarpine and timolol maleate ophthalmic solutions, Δ9-tetrahydrocannabinol-valine-hemisuccinate SLNs produced a greater effect on IOP in terms of both intensity and duration. In terms of tissue concentrations, significantly higher concentrations of Δ9-tetrahydrocannabinol-valine-hemisuccinate were observed in iris-ciliary bodies and retina-choroid with SLNs.

CONCLUSION:

Δ9-Tetrahydrocannabinol-valine-hemisuccinate formulated in a lipid-based nanoparticulate carrier shows promise in glaucoma pharmacotherapy.

TRANSLATIONAL RELEVANCE:

Glaucoma therapies usually focus on decreased aqueous humor production and increased outflow. However, such therapy is not curative, and there lies a need in preclinical research to focus efforts on agents that not only affect the aqueous humor dynamics but also provide neuroprotection. Historically, there have been bench-scale studies looking at retinal ganglion cell death post-axonal injury. However, for a smooth translation of this in vitro activity to the clinic, animal models examining IOP reduction, i.e., connecting the neuroprotective activity to a measurable outcome in glaucoma management (IOP), need to be investigated. This study investigated the IOP reduction efficacy of cannabinoids for glaucoma pharmacotherapy in a normotensive rabbit model, bringing forth a new class of agents with the potential of IOP reduction and improved permeation to the back of the eye, possibly providing neuroprotective benefits in glaucoma management.”

https://www.ncbi.nlm.nih.gov/pubmed/31588378

“THC has been demonstrated to be effective in glaucoma management, helping to lower IOP in human subjects after smoking marijuana; however, the molecule fails to manifest a similar effect when dosed topically. This research explores molecular bioengineering and formulation-based strategies to improve the ocular bioavailability of THC, facilitating the molecule to translate into a dosage form capable of demonstrating a desired IOP-lowering effect even on topical application. These studies suggest that formulation development efforts along with prodrug derivatization can effectively improve the overall ocular bioavailability of THC. Thus, THC-VHS represents a potential new therapy option for the treatment and management of glaucoma by virtue of its superiority in lowering IOP when compared to antiholinergic and beta blockers, as studied in this model.”
https://tvst.arvojournals.org/article.aspx?articleid=2751570

Role of Cannabinoids and Terpenes in Cannabis-Mediated Analgesia in Rats.

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View details for Cannabis and Cannabinoid Research cover image

“Cannabis sativa has been used for centuries in treating pain. However, the analgesic role of many of its constituents including terpenes is unknown. This research examined the contributions of terpenes (volatile oil) and cannabinoids in cannabis-mediated analgesia in rats.

Methods: Animals received intraperitoneal administration of either vehicle, 10.0 or 18.0 mg/kg morphine, or various doses of the extract without terpenes, isolated terpenes, Δ9-tetrahydrocannabinol (THC), or the full extract. Thirty minutes later animals were tested on hotplate and tail-flick tests of thermal nociception. One week later, rats received a second administration of test articles and were tested 30 min later in the abdominal writhing test of inflammatory nociception.

Results: In the thermal assays, hotplate and tail-flick latencies for morphine-treated rats were dose dependent and significantly higher than vehicle-treated animals. All the cannabinoid compounds except for the isolated terpenes produced dose-dependent increases in hotplate and tail-flick latencies. In the inflammatory nociceptive assay, animals treated with vehicle and isolated terpenes demonstrated increased abdominal writhing, whereas all the cannabinoid compounds significantly decreased abdominal writhing responses.

Conclusions: Overall, THC alone produced robust analgesia equivalent to the full cannabis extract, whereas terpenes alone did not produce analgesia. These data suggest the analgesic activity of cannabis is largely mediated by THC, whereas terpenes alone do not cause alterations in cannabis-mediated analgesia.”

https://www.ncbi.nlm.nih.gov/pubmed/31579834

“The work herein demonstrates that cannabis extracts can not only produce robust analgesia without the terpene-containing volatile oils, but isolated THC appears to be all that is required to produce such effects.”

https://www.liebertpub.com/doi/10.1089/can.2018.0054

How does cannabidiol (CBD) influence the acute effects of delta-9-tetrahydrocannabinol (THC) in humans? A systematic review.

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Neuroscience & Biobehavioral Reviews“The recent liberalisation of cannabis regulation has increased public and scientific debate about its potential benefits and risks. A key focus has been the extent to which cannabidiol (CBD) might influence the acute effects of delta-9-tetrahydrocannabinol (THC), but this has never been reviewed systematically. In this systematic review of how CBD influences the acute effects of THC we identified 16 studies involving 466 participants. Ten studies were judged at low risk of bias. The findings were mixed, although CBD was found to reduce the effects of THC in several studies. Some studies found that CBD reduced intense experiences of anxiety or psychosis-like effects of THC and blunted some of the impairments on emotion and reward processing. However, CBD did not consistently influence the effects of THC across all studies and outcomes. There was considerable heterogeneity in dose, route of administration and THC:CBD ratio across studies and no clear dose-response profile emerged. Although findings were mixed, this review suggests that CBD may interact with some acute effects of THC.”

https://www.ncbi.nlm.nih.gov/pubmed/31580839

“CBD influenced the effects of THC in some but not all studies. Several studies found that CBD reduced the acute effects of THC. CBD may reduce intense experiences of anxiety or psychosis-like effects of THC. CBD may blunt effects of THC on emotion and reward processing. CBD did not alter subjective intoxication or psychomotor effects of THC. CBD may influence the benefits and harms of cannabis”

https://www.sciencedirect.com/science/article/pii/S0149763419305615?via%3Dihub