CNR1 and FAAH variation and affective states induced by marijuana smoking

Background: Polymorphisms in cannabinoid receptor type 1 (encoded by CNR1) and fatty acid amide hydrolase (encoded by FAAH) have been associated with cannabis dependence, but it remains unknown whether variation within these genes influences cannabis’ acute effects on affect.

Objective: Conduct a secondary data analysis study to determine whether previously observed acute effects of tetrahydrocannabinol (THC) on mood was dependent upon variation in CNR1 and FAAH.

Methods: A balanced placebo design was used crossing marijuana administration (i.e., 0% THC vs. 2.8% THC) with stimulus expectancy. Participants (N = 118; 64% male) provided DNA and completed the Profile of Mood States questionnaire prior to and after smoking. Haplotypes were constructed from genotyped single nucleotide polymorphisms for CNR1 (rs1049353 and rs806368) and FAAH (rs4141964, rs324420, and rs11576941); rs2023239 (CNR1) and rs6703669 (FAAH) were not part of a phased haplotype block. Analyses tested both main and interaction effects for genotype across CNR1 and FAAH, and drug, and expectancy effects.

Results: THC increased levels of POMS Tension-Anxiety and Confusion-Bewilderment over and above the effects of variation in CNR1 and FAAH. Significant drug X genotype/haplotype and expectancy X genotype/haplotype interaction effects were observed for some but not all mood states [e.g., ‘C’ allele carriers of rs2023239 who received THC had higher levels of Anger-Hostility (β= 0.29 (0.12), p= .02) compared to those who received placebo].

Conclusion: These preliminary findings suggest individual differences in mood states after using marijuana depend on genetic variation. Such information might be useful in understanding either motivation for use of marijuana and/or risk for associated behaviors.     

Inflammaging and Cannabinoids

Aging is a complex phenomenon associated with a wide spectrum of physical and physiological changes affecting every part of all metazoans, if they escape death prior to reaching maturity. Critical to survival, the immune system evolved as the principal component of response to injury and defense against pathogen invasions. Because how significantly immune system affects and is affected by aging, several neologisms now appear to encapsulate these reciprocal relationships, such as Immunosenescence. The central part of Immunosenescence is Inflammaging –a sustained, low-grade, sterile inflammation occurring after reaching reproductive prime. Once initiated, the impact of Inflammaging and its adverse effects determine the direction and magnitudes of further Inflammaging. In this article, we review the nature of this vicious cycle, we will propose that phytocannabinoids as immune regulators may possess the potential as effective adjunctive therapies to slow and, in certain cases, reverse the pathologic senescence to permit a more healthy aging.     

火麻油软胶囊润肠通便作用的实验研究

目的研究火麻油软胶囊对正常鼠的润肠通便作用。方法应用肠管在体实验法,观察比较小鼠或大鼠的肠炭粉推进百分率、排泄量、小肠容积、回肠蠕动和黏膜充血情况等指标。结果排粪便数增多,排便时间提前,小肠推进率提高,增加小肠容积,回肠蠕动增强,肠黏膜无充血变红现象、油光明显。结论火麻油软胶囊具有较好的润肠通便作用。     

Cannabis smoking and lung cancer risk: Pooled analysis in the International Lung Cancer Consortium

To investigate the association between cannabis smoking and lung cancer risk, data on 2,159 lung cancer cases and 2,985 controls were pooled from 6 case‐control studies in the US, Canada, UK, and New Zealand within the International Lung Cancer Consortium. Study‐specific associations between cannabis smoking and lung cancer were estimated using unconditional logistic regression adjusting for sociodemographic factors, tobacco smoking status and pack‐years; odds‐ratio estimates were pooled using random effects models. Subgroup analyses were done for sex, histology and tobacco smoking status. The shapes of dose‐response associations were examined using restricted cubic spline regression. The overall pooled OR for habitual versus nonhabitual or never users was 0.96 (95% CI: 0.66–1.38). Compared to nonhabitual or never users, the summary OR was 0.88 (95%CI: 0.63–1.24) for individuals who smoked 1 or more joint‐equivalents of cannabis per day and 0.94 (95%CI: 0.67–1.32) for those consumed at least 10 joint‐years. For adenocarcinoma cases the ORs were 1.73 (95%CI: 0.75–4.00) and 1.74 (95%CI: 0.85–3.55), respectively. However, no association was found for the squamous cell carcinoma based on small numbers. Weak associations between cannabis smoking and lung cancer were observed in never tobacco smokers. Spline modeling indicated a weak positive monotonic association between cumulative cannabis use and lung cancer, but precision was low at high exposure levels. Results from our pooled analyses provide little evidence for an increased risk of lung cancer among habitual or long‐term cannabis smokers, although the possibility of potential adverse effect for heavy consumption cannot be excluded.     

The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS)

Objective: To test whether cannabinoids reduce urge incontinence episodes without affecting voiding in patients with multiple sclerosis. This was part of the multicentre trial of the Cannabinoids in Multiple Sclerosis (CAMS) study. Subjects and methods: The CAMS study randomised 630 patients to receive oral administration of cannabis extract, Δ⁹-tetrahydrocannabinol (THC) or matched placebo. For this substudy subjects completed incontinence diaries. Results: All three groups showed a significant reduction, p<0.01, in adjusted episode rate (i.e. correcting for baseline imbalance) from baseline to the end of treatment: cannabis extract, 38%; THC, 33%; and placebo, 18%. Both active treatments showed significant effects over placebo (cannabis extract, p=0.005; THC, p=0.039). Conclusion: The findings are suggestive of a clinical effect of cannabis on incontinence episodes in patients with MS. This is in contrast to the negative finding of the CAMS study, where no difference was seen in the primary outcome of spasticity.     

Facilitation of brain stimulation reward byΔ 9-tetrahydrocannabinol

The present experiment explored whetherΔ ⁹-tetrahydrocannabinol (Δ ⁹-THC), the psychoactive ingredient in marijuana, shares with other drugs of abuse the ability to facilitate brain stimulation reward acutely, as measured by clectrical intracranial self-stimulation (ICSS). Laboratory rats were implanted with stimulation electrodes in the medial forebrain bundle, and trained to stable performance on a self-titrating threshold ICSS paradigm.Δ ⁹-THC, at a dose believed pharmacologically relevant to moderate human use of marijuana, acutely lowered ICSS thresholds, suggesting that marijuana acts on similar CNS hedonic systems to most other drugs of abuse.