Tag Archives: tetrahydrocannabinol

Pre- and post-conditioning treatment with an ultra-low dose of Δ9-tetrahydrocannabinol (THC) protects against pentylenetetrazole (PTZ)-induced cognitive damage.

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Behavioural Brain Research

“Preconditioning, a phenomenon where a minor noxious stimulus protects from a subsequent more severe insult, and post-conditioning, where the protective intervention is applied following the insult, offer new insight into the neuronal mechanism(s) of neuroprotection and may provide new strategies for the prevention and treatment of brain damage. We have previously reported that a single administration of an extremely low dose of Δ(9)-tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) to mice induced minor long-lasting cognitive deficits.

In the present study we examined the possibility that such a low dose of THC will protect the mice from more severe cognitive deficits induced by the epileptogenic drug pentylenetetrazole (PTZ). THC (0.002 mg/kg, a dose that is 3-4 orders of magnitude lower than the doses that induce the conventional effects of THC) was administered 1-7 days before, or 1-3 days after the injection of PTZ (60 mg/kg). The consequences of this treatment were studied 3-7 weeks later by various behavioral tests that evaluated different aspects of memory and learning.

We found that a single administration of THC either before or after PTZ abolished the PTZ-induced long-lasting cognitive deficits.

Biochemical studies indicated a concomitant reduction in phosphorylated-ERK (extracellular signal-regulated kinase) in the cerebella of mice 7 weeks following the injection of THC.

Our results suggest that a pre- or post-conditioning treatment with extremely low doses of THC, several days before or after brain injury, may provide safe and effective long-term neuroprotection.”

https://www.ncbi.nlm.nih.gov/pubmed/21315768

https://www.sciencedirect.com/science/article/pii/S0166432811001094?via%3Dihub

Future Aspects for Cannabinoids in Breast Cancer Therapy.

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“Cannabinoids (CBs) from Cannabis sativa provide relief for tumor-associated symptoms (including nausea, anorexia, and neuropathic pain) in the palliative treatment of cancer patients.

Additionally, they may decelerate tumor progression in breast cancer patients.

Indeed, the psychoactive delta-9-tetrahydrocannabinol (THC), non-psychoactive cannabidiol (CBD) and other CBs inhibited disease progression in breast cancer models.

The effects of CBs on signaling pathways in cancer cells are conferred via G-protein coupled CB-receptors (CB-Rs), CB1-R and CB2-R, but also via other receptors, and in a receptor-independent way.

THC is a partial agonist for CB1-R and CB2-R; CBD is an inverse agonist for both.

In breast cancer, CB1-R expression is moderate, but CB2-R expression is high, which is related to tumor aggressiveness. CBs block cell cycle progression and cell growth and induce cancer cell apoptosis by inhibiting constitutive active pro-oncogenic signaling pathways, such as the extracellular-signal-regulated kinase pathway.

They reduce angiogenesis and tumor metastasis in animal breast cancer models. CBs are not only active against estrogen receptor-positive, but also against estrogen-resistant breast cancer cells. In human epidermal growth factor receptor 2-positive and triple-negative breast cancer cells, blocking protein kinase B- and cyclooxygenase-2 signaling via CB2-R prevents tumor progression and metastasis.

Furthermore, selective estrogen receptor modulators (SERMs), including tamoxifen, bind to CB-Rs; this process may contribute to the growth inhibitory effect of SERMs in cancer cells lacking the estrogen receptor.

In summary, CBs are already administered to breast cancer patients at advanced stages of the disease, but they might also be effective at earlier stages to decelerate tumor progression.”

 https://www.ncbi.nlm.nih.gov/pubmed/30987191
https://www.mdpi.com/1422-0067/20/7/1673

Δ9-tetrahydrocannabinol attenuates oxycodone self-administration under extended access conditions.

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Neuropharmacology

“Growing nonmedical use of prescription opioids is a global problem, motivating research on ways to reduce use and combat addiction.

Medical cannabis (“medical marijuana”) legalization has been associated epidemiologically with reduced opioid harms and cannabinoids have been shown to modulate effects of opioids in animal models.

This study was conducted to determine if Δ9-tetrahydrocannabinol (THC) enhances the behavioral effects of oxycodone.

Together these data demonstrate additive effects of THC and oxycodone and suggest the potential use of THC to enhance therapeutic efficacy, and to reduce the abuse, of opioids.”

https://www.ncbi.nlm.nih.gov/pubmed/30980837

“Δ9-tetrahydrocannabinol (THC) enhances the antinociceptive effects of oxycodone. Vaporized and injected THC reduces oxycodone self-administration. Cannabinoids may reduce opioid use for analgesia. Cannabinoids may reduce nonmedical opioid use.”  

https://www.sciencedirect.com/science/article/pii/S0028390819301212?via%3Dihub

Prescription of a THC/CBD-Based Medication to Patients with Dementia: A Pilot Study in Geneva

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“Dementia is increasing worldwide. No effective medication is currently available for the treatment of the underlying disease and accompanying behavioral symptoms. Cannabinoids might have a beneficial effect, but clinical studies with (low-dose) synthetic THC have not been conclusive.

Objective: To test the acceptability, practical aspects, and clinical outcomes of the introduction of a THC/CBD-based oral medication in severely demented patients in a specialized nursing home in Geneva.

Methods: This was a prospective observational study.

Results: Ten female demented patients with severe behavior problems received oral medication with on average 7.6 mg THC/13.2 mg CBD daily after 2 weeks, 8.8 mg THC/17.6 mg CBD after 1 month, and 9.0 mg THC/18.0 mg CBD after 2 months. The THC/CBD-based oil was preferred. Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory score, and a behavior problem visual analog scale decreased by 40% after 2 months, rigidity score by 50%. Half of the patients decreased or stopped other psychotropic medications. The staff appreciated the decrease in rigidity, making daily care and transfers easier, the improved direct contact with the patients, the improvement in behavior, and the decrease in constipation with less opioids. There was no withholding of the medication for reasons of side effects, and the effects persisted after 2 months.

Conclusions: An oral cannabis extract with THC/CBD, in higher dosages than in other studies, was well tolerated and greatly improved behavior problems, rigidity, and daily care in severely demented patients.”

https://www.karger.com/Article/Abstract/498924

Enhancing effects of acute exposure to cannabis smoke on working memory performance

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Neurobiology of Learning and Memory

“Prior preclinical studies show that acute cannabinoid injections impair cognition.

Here, effects of cannabis smoke on working memory were tested in rats.

Cannabis smoke improved working memory accuracy.

Placebo smoke did not affect working memory accuracy.

Enhancing effects are likely due to THC dose and/or route of administration.”  https://www.sciencedirect.com/science/article/pii/S1074742718302776?via%3Dihub

“Numerous preclinical studies show that acute cannabinoid administration impairs cognitive performance. Almost all of this research has employed cannabinoid injections, however, whereas smoking is the preferred route of cannabis administration in humans. The goal of these experiments was to systematically determine how acute exposure to cannabis smoke affects working memory performance in a rat model.

Exposure to cannabis smoke had no effect on male rats’ performance, but surprisingly, enhanced working memory accuracy in females, which tended to perform less accurately than males under baseline conditions. In addition, cannabis smoke enhanced working memory accuracy in a subgroup of male rats that performed comparably to the worst-performing females. Exposure to placebo smoke had no effect on performance, suggesting that the cannabinoid content of cannabis smoke was critical for its effects on working memory.” https://www.ncbi.nlm.nih.gov/pubmed/30521850

 

Bronchodilator effect of delta1-tetrahydrocannabinol.

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“1 delta1-trans-tetrahydrocannabinol, (delta1-THC) produces bronchodilatation in asthmatic patients. 2 Administered in 62 microliter metered volumes containing 50–200 microgram by inhalation from an aerosol device to patients judged to be in a steady state, it increased peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1). 3 The rate of onset, magnitude, and duration of the bronchodilator effect was dose related.”

https://www.ncbi.nlm.nih.gov/pubmed/656294

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1429361/

“Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients. The mode of action of THC differs from that of sympathomimetic drugs, and it or a derivative may make a suitable adjuvant in the treatment of selected asthmatics.” https://www.ncbi.nlm.nih.gov/pubmed/797044

“Bronchodilators are medications that open (dilate) the airways (bronchial tubes) of the lung by relaxing bronchial muscles and allow people who have difficulty breathing to breath better. Bronchodilators are used for treating:

https://www.medicinenet.com/bronchodilators_for_asthma/article.htm

Daily Practice Managing Resistant Multiple Sclerosis Spasticity With Delta-9-Tetrahydrocannabinol: Cannabidiol Oromucosal Spray: A Systematic Review of Observational Studies.

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 Image result for journal of central nervous system disease“Spasticity is one of the most common symptoms in people with multiple sclerosis (MS). Conventional anti-spasticity agents have limitations in their efficacy and tolerability.

Delta-9-tetrahydrocannabinol: cannabidiol (THC:CBD) spray, a cannabinoid-based medicine, is approved as an add-on therapy for MS spasticity not adequately controlled by other anti-spasticity medications. The results from randomized controlled trials (RCTs) have demonstrated a reduction in the severity of spasticity and associated symptoms. However, RCTs do not always reflect real-life outcomes. We systematically reviewed the complementary evidence from non-interventional real-world studies.

METHODS:

A systematic literature review was conducted to identify all non-RCT publications on THC:CBD spray between 2011 and 2017. Data on study design, patient characteristics, effectiveness, and safety outcomes were extracted from those publications meeting our inclusion criteria.

RESULTS:

In total, we reviewed 14 real-world publications including observational studies and treatment registries. The proportion of patients reaching the threshold of minimal clinical important difference (MCID), with at least a 20% reduction of the spasticity Numeric Rating Scale (NRS) score after 4 weeks ranged from 41.9% to 82.9%. The reduction in the mean NRS spasticity score after 4 weeks was maintained over 6-12 months. The average daily dose was five to six sprays. Delta-9-tetrahydrocannabinol: cannabidiol was well tolerated in the evaluated studies in the same way as in the RCTs. No new or unexpected adverse events or safety signals were reported in everyday clinical practice.

CONCLUSIONS:

The data evaluated in this systematic review provide evidence for the efficacy and safety of THC:CBD in clinical practice and confirm results obtained in RCTs.”

https://www.ncbi.nlm.nih.gov/pubmed/30886530

https://journals.sagepub.com/doi/10.1177/1179573519831997

Beneficial and deleterious effects of cannabinoids in the brain: the case of ultra-low dose THC.

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Publication Cover

“This article reviews the neurocognitive advantages and drawbacks of cannabinoid substances, and discusses the possible physiological mechanisms that underlie their dual activity. The article further reviews the neurocognitive effects of ultra-low doses of ∆9-tetrahydrocannabinol (THC; 3-4 orders of magnitude lower than the conventional doses) in mice, and proposes such low doses of THC as a possible remedy for various brain injuries and for the treatment of age-related cognitive decline.”

https://www.ncbi.nlm.nih.gov/pubmed/30864864

https://www.tandfonline.com/doi/abs/10.1080/00952990.2019.1578366?journalCode=iada20

Cannabinoid Use in Patients With Gastroparesis and Related Disorders: Prevalence and Benefit.

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Image result for Am J Gastroenterol.

“Gastroparesis (Gp) can be a challenging disorder to manage due to the paucity of treatment options. We do not know how frequently patients with Gp symptoms resort to cannabinoids to address their symptoms. This study (i) determines the prevalence of cannabinoid use in patients with Gp symptoms, (ii) describes the patients with Gp symptoms using cannabinoids, and (iii) assesses the patients’ perceived benefit of cannabinoids for Gp symptoms.

METHODS:

Consecutive outpatients with symptoms suggestive of Gp seen on follow-up at our academic center from June 2018 to September 2018 filled out questionnaires on their symptoms and the current treatments.

RESULTS:

Of 197 patients, nearly half (n = 92, 46.7%) reported current (35.5%) or past (11.2%) use of cannabinoids, including tetrahydrocannabinol (n = 63), dronabinol (n = 36), and/or cannabidiol (n = 16). Of these, most perceived improvement in Gp symptoms from cannabinoids (93.5% with tetrahydrocannabinol, 81.3% with cannabidiol, and 47.2% with dronabinol). Cannabinoids were used most commonly via smoking (n = 46). Patients taking cannabinoids were younger (41.0 ± 15.4 vs 48.0 ± 15.9 years; P < 0.01) and had a higher Gastroparesis Cardinal Symptom Index total score (3.4 ± 1.0 vs 2.8 ± 1.3; P < 0.01) compared with patients with no history of cannabinoid use.

CONCLUSIONS:

A third of patients with Gp symptoms actively use cannabinoids for their chronic symptoms. Most of these patients perceive improvement in their symptoms with cannabinoids. Patients taking cannabinoids were younger and more symptomatic than those not taking cannabinoids. Further studies on the efficacy and safety of cannabinoids in Gp will be useful.”

https://www.ncbi.nlm.nih.gov/pubmed/30865015

https://journals.lww.com/ajg/Abstract/2019/06000/Cannabinoid_Use_in_Patients_With_Gastroparesis_and.23.aspx

Promoting cannabis products to pharmaceutical drugs.

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European Journal of Pharmaceutical Sciences

“Cannabis sativa is widely used for medical purposes. However, to date, aroma, popular strain name or the content of two phytocannabinoids-Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are mostly considered for therapeutic activity. This is despite the hundreds of compounds in this plant and their potential synergistic interactions in mixtures. New, specific and effective cannabis-based drugs must be developed to achieve adequate medical standards for the use of cannabis. To do this, the comprehensive molecular profile of cannabis-based drugs must be defined, and mixtures of compounds should be tested for superior therapeutic activity due to synergistic effects compared to individually isolated cannabis compounds. The biological pathways targeted by these new drugs should also be characterized more accurately. For drug development and design, absorption, distribution, metabolism and elimination versus toxicity (ADME/Tox) must be characterized, and therapeutic doses identified. Promoting the quality and therapeutic activity of herbal or synthetic cannabis products to pharma grade is a pressing need worldwide.”

https://www.ncbi.nlm.nih.gov/pubmed/30851400

https://www.sciencedirect.com/science/article/pii/S0928098719300880?via%3Dihub