Archive for the ‘Contributing Author: Jahan Marcu’ Category
Saturday, February 27th, 2010
Clara Tourino, Andreas Zimmer, and Olga Valverde published a provacative article demonstrating that THC can protect against MDMA (ecstasy) induced brain damage. The authors note that the negative effects of long term MDMA use arise from it’s metabolism. High temperatures cause “the formation and uptake of MDMA toxic metabolites that increase oxidative stress, causing nerve terminal damage…and eventually axonal degeneration.”
Basically current research suggests that taking MDMA (ecstasy) and going dancing may increase brain damage associated with long term use.
The authors also site evidence that MDMA is often consumed with cannabis (1) (2). They point out that THC has been widely reported to lower body temperature, decrease inflammation, and is a potent anti-oxidant. Interestingly, in animal models of drug abuse THC and MDMA appear to “counter balance” each other. THC is able to attenuate many effects of MDMA including hyperthermia (overheating), hyper-locomotion, and anxiety. However, these authors are the first to explore if THC can actually protect brain cells from MDMA’s toxic effects.
Below is a figure from the publication:
This image shows a vehicle or untreated brain compared to MDMA and THC treated brains. Notice the pale complexion of the MDMA brain slice? This decrease in staining indicates a reduction in important brain proteins, this unwanted protein reduction is prevented when THC is given to the mice.
They also discuss some of the implications of their findings:
“The frequent co-use of both drugs makes it particularly interesting to study the effects of their combination Indeed, previous studies describe the effects of THC and MDMA together in animal models of locomotor activity, temperature, anxiety, reward and THC-dependence. However, the neuroprotective effects of THC on MDMA neurotoxicity have never been reported. In addition, the dose of THC used in this study (3 mg/kg, i.p.) could be considered a dose consumed by regular moderate cannabis users, and for that reason similar doses are used in the previously reported animal studies.”
So what does this mean to humans?
A few clinical studies on polydrug use have shown that use of cannabis and MDMA leads to deficits in brain function. Yet, the authors point to three studies which suggest that MDMA users that also consume THC have less ‘brain problems’ than “pure MDMA users.” (1) (2) (3)
MDMA also has a therapeutic role in diseases such as PTSD. Given that THC may reduce possible negative effects associated with MDMA use, i.e., hyperthermia and listening to techno music. Future clinical studies that are examining a therapeutic role for MDMA, should consider including groups of patients that receive a measured dose of both drugs.
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Friday, February 19th, 2010
The Los Angeles Times, Sacramento Bee, and the Associated press published articles on studies showing that Cannabis has therapeutic value. The studies were conducted through the Center for Medicinal Cannabis Research (CMCR) at the University of San Diego. The CMCR was created in 2000 to answer the question, “Does Marijuana have Therapeutic Value?”
The CMCR have submitted their report to the legislature and Governor of California, in which the authors claim to “have found reasonable evidence that cannabis is a promising treatment.”
The CMCR report is a summary of the clinical trials on smoked or vaporized cannabis that were conducted by the organization. Basically, the organization spent 10 million dollars and completed 6 clinical trials. These trials demonstrate that cannabis is an effective pain medicine for MS and HIV/AIDS patients. Notably, one study showed that ”low potency” cannabis may be effective at reducing pain with out inducing a “high”.
The CMCR had to overcome numerous setbacks. At least 5 clinical trials were canceled for various reasons. In one instance a clinical trial on chemotherapy induced nausea and vomiting had to be cancelled because not enough cancer patients could be recruited. Additionally, the approval of a study by the government typically took 18 months.
The Full Report may be downloaded here: http://www.cmcr.ucsd.edu/CMCR_REPORT_FEB17.pdf
The Press Release can be viewed here: http://health.ucsd.edu/news/2010/2-17-medical-marijuana.htm
Elsewhere, the Iowa Pharmacy Board is already expecting cannabis to available as a medicine soon. As the board has recommended to legislators that cannabis be rescheduled to allow medical use. Could Iowa potentially distribute cannabis through a pharmacy? Not unless cannabis is removed from schedule I.
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Saturday, February 6th, 2010
A growing body of scientific research suggests that cannabinoid receptors or the endocannabinoid system may have a therapeutic role in major depression (MD) and/or bipolar disorder (BD). A paper published in “Pharmaceutic Research” demonstrated that certain variations or mutations associated with the Endocannabinoid system may make humans more susceptible to MD or BD. The current study found that specific mutations in both the CB1 receptor and FAAH enzyme, were found in human subjects suffering from MD and BP. Interestingly, only the CB1 receptor mutations were linked to Major Depression, while both CB1 receptor and FAAH mutations were found patients suffering from bipolar disorders
What is the Endocannabinoid system (ECS)? And why is it linked to emotion?
The ECS is comprised of two receptors, the CB1 and CB2 receptor. The CB1 receptor is perhaps one of the most abundant receptors in the human brain. It is found in high amounts in many areas of the human brain, including parts of the brain important for emotion. It is fairly common knowledge that THC, from the cannabis plant, can activate CB1 receptors. However, humans and many other animals also make a “natural THC” called Anandamide. Anandamide is synthesized by cells in our body, and can impact a variety of natural processes such as eating, sleeping, memory, energy, and mood. Once Anandamide is synthesized it will be degraded or destroyed by another protein FAAH. The enzyme activity or the rate at which FAAH destroys Anandamide will indirectly affect the level of CB1 activity.
So, if FAAH is over active there will be fewer signals in the brain telling you to eat and sleep, among other things. If there is not enough FAAH, it will make a person hungry.
Mutations in FAAH or cannabinoid receptors may underlie many diseases; in fact a “Clinical Endocannabinoid Deficiency” has already been proposed to explain some chronic diseases such as “migraines, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis“. A previous study has also linked variations in FAAH and CB1 rceptors to anorexia nervosa and bulimia nervosa.
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Thursday, November 12th, 2009
Scientists think the most abundant ingredients in tea may mediate activity of cannabinoid receptors. Polyphenols are the most abundant ingredient found in tea leaves. The average western diet usually includes at least 50mg of these polyphenols, the “mediterranean” diet contains at least twice this amount. Polyphenols such as catechins are known for their numerous health benefits including nueroprotection, anti-inflammatory properties, and appetite modulation. These health benefits manifest as reducing the chance of a stroke, slowing cognitive decline, and protecting against obesity. However, there is considerable disagreement on how these polyphenols cause these effects, for instance these researchers hypothesize that these compounds interact with cannabinoid receptor signalling.
Upon analysis the authors found that the compounds in tea actually bind both types of cannabinoid receptors, with notable higher affinity for the CB1 receptor. However, the receptor binding affinity of these polyphenols was relatively weak compared to a synthetic cannabinoid, CP55,940.
The authors speculate, “Signal strength may be amplified in vivo by non-receptor related mechanisms, i.e. Fatty acid amide hydrolase(FAAH)…” Meaning, the combination of polyphenols may activate many things at once in humans. FAAH would be an interesting target because the inhibition of this enzyme makes the levels of endocannabinoids rise.
Will Tea drinking or tea extracts be prohibited because of cannabinoid receptor activity? Does this mean Tea will become a schedule I drug like cannabis? Will 4:20 become the new tea time? Probably not. This is not the first evidence for cannabinoids as part of the human diet. Beta-caryophyllene can activate the CB2 receptor, and it is FDA approved.
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Saturday, October 17th, 2009
Women and men percieve and respond to cannabis differently. Interesting gender differences are begining to be uncovered through animal studies, drug surveys, and clinical trials. Here are a few differences that have been published recently:
- Notably, estrogen can attenuate or inhibit various cannabinoid induced homeostatic changes such as appetite, body temperature, and brain activity.In other words, estrogen may allow women to be less susceptible to effects from cannabis or other cannabinoid medicines. Implying women can handle the effects of the drug better than men. Shel Silverstein’s “Smoke Off” provides a good analogy.
- In animal studies (Review, Original research Article) on mice without the type 1 cannabinoid receptor (CB1), there appears to be a gender dependent phenotype. Male mice develop “strange” bones earlier, resulting from the removal of the CB1 receptor. In the first few weeks of life ,male mice without this receptor have remarkably higher bone volume. However, both genders develop severe age related osteoporosis later in life. It is also interesting to note, that this gender disparity is not observed in all transgenic mice without cannabinoid receptors–only in mice missing the CB1 receptor. Mice without the CB2 receptor have equally bad bones; gender independent effects.
- The ‘putative’ cannabinoid receptor GPR55, also displays similar gender dependent effects. When knocked out or removed from mice, the males have higher bone mass or volume compared to females.
- Another study completed at Temple Medical School in Philadelphia also showed sex dependent differences in mice without CB1 receptors. These differences were in reward seeking behaviors when it comes to cocaine and food. Basically male mice without CB1 self administer less cocaine and and less sweet food (Ensure). This research suggests that the cannabinoid system modulates appetite differently between genders.
- Drug abuse surveys have shown that women and men endorse different issues when it comes to cannabis use and abuse
As new cannabinid drugs are brought to market, and cannabis is becoming available in pharmacies around the world; more research is needed which tracks potential gender differences in response to cannabinoids.
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Tuesday, September 15th, 2009
A recent animal study out of Australia showed for the first time that food deprivation and stress hormones may enhance the release of THC stored in fat, thus increasing the amount of cannabinoids in the blood. The results may provide a mechanism for so called “Cannabis Flashbacks,” explaining instances where ex-cannabis users that were exposed to stress or under went weight loss, tested positive for THC.
THC is a lipophillic, fat loving or fat-like compound, that is rapidly absorbed or stored in fat. Interestingly, some researchers have discovered that THC accumulates in rodent gonadal fat tissue (epididymal) at higher levels than any other fatty tissue including the brain and liver (Ravitch 1979). In, humans it is still somewhat unclear where most of the THC gathers for its stay in the body. The precise mechanism whereby THC is released from fat is unknown but it appears THC is NOT metabolized in fat. THC is degraded by the liver to the excreted product: 11-Hydroxy-THC. Furthermore, THC has been found in fat 28 days since the last exposure. This long term storage of THC is consistent with observations that users can test positive after 77 days at levels >20ng/ml (Ellis et al 1985).
The authors suggest that it could be possible for THC to cause intoxication after being stored and released from fat. However,several things can cause THC release: stress,food deprivation, weight loss, exercise, physical or mental stress. However, MUCH MORE research is need in order to determine if it’s even possible to cause a measurable intoxication. Important questions remain like, “What’s the difference between a ‘perma-high‘ and a ‘cannabis flashback’? Will eating a lot of food and remaining sedentary help you test negative for THC? And if THC intoxication can occur from physical activity, then could Santonio Holmes have caught the winning pass in super bowl 43 while intoxicated?…similar analogies apply to Ricky Williams, Rob Van Dam, Michael Phelps, and other professional athletes.
Eating your way through a drug test is an attractive speculation. However, it would olny work if it was balanced with remaining abstinent from cannabis use.
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Saturday, August 22nd, 2009
On August 20th 2009, researchers from Italy published an article in the Journal of Molecular Medicine on the benefits of cannabidiol (CBD) to treat Inflammatory bowel disease (IBD), in a mouse model of colitis. CBD dramatically reduced tissue damage and inflammation in vivo.
The research team showed, for the first time that CBD reduced radical oxygen species (ROS) and lipid peroxidation in intestinal cells of mice. ROS production is a hallmark of IBD, as oxidative stress is the leading tissue destructive force that contributes to the development of IBD. The article also features pictures of treated and untreated intestinal tissue.
Of additional interest is the pharmacology of CBD. CBD was most effective at 5mg/kg. However, there wasn’t much difference at higher doses, even a dose of 10mg/kg did not exert a further protective effect. Lower doses (1-2.5mg/kg) were not significantly effective.
Also, the researchers found that CBD inhibited Nitric Oxide Synthase, an enzyme with produces Nitric oxide (NO). High levels of NO correlate correlate well with IBD activity, and previous experiments have shown that other Nitric Oxide Synthase Inhibitors can also improve symptoms of IBD.
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