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.
Posted in Contributing Author: Jahan Marcu | No Comments »
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.
Posted in Cannabination, Contributing Author: Jahan Marcu | No Comments »
Tuesday, August 4th, 2009
In the journal of Clincal Pyschopharmacology, a research team reports on the improvement of schizophrenic symptoms in a small group of patients who were treated with pure Delta9-THC (Marinol AKA Dronabinol). The doctors sought out patients who had chronic refractory schizophrenia and had a documented history of cannabis use. After going through about 200 patients, the doctors found a total of 6 that met the criteria.
Generally, cannabinoids are associated with the worsening of psychotic symptoms. So, why did Doctors give THC, the main ingredient in cannabis, to a group of patients who had severe cases of mental illness?
The authors write, “The idea for our use of dronabinol in this population came from the surprisingly good response of 1 patient. He was grossly psychotic, assaultive, disorganized, and highly refractory to multiple medication trials. However, in reviewing his history, we noted that he had a history of several years of calm behavior when he was using marijuana.”
After treatment with pure THC the authors note, ” Remarkably, he became calm, logical, nonviolent, and cooperative within days and was discharged within weeks. This prompted us to try dronabinol on other patients who fit this profile: having a diagnosis of chronic refractory schizophrenia, together with a history of marijuana use during which they reported some improvement.”
In regards to the safety profile of synthetic THC, the author’s comment that it “does not seem to have significant addictive potential or withdrawal in clinical practice.”
These results are remarkable patients with refractory schizophrenia because current interventions and treatments rarely succeed. These patients were also unresponsive to standard dopamine blockers, thus the abnormalities could lay in a non-dopamine system, i.e, the endocannabiod system. Perhaps the abnormalities may be related to the endocannabinoid deficiency theory. Since there is no viable treatment–there us an urgent need to find and develop medications for this patient population.
Additionally, these results go against the current accepted theory that activating the cannabinoid receptors (CB1) should worsen psychotic symptoms and blocking the receptor should improve it. Another piece of supporting evidence against this theory, comes from a clinical trial with Rimonabant, a CB1 Receptor Blocker. CB1 Blockers prevent other compunds from activating the receptor, thus limiting the activity of the receptor. The Cb1 receptor blocker did not improve symptoms.
The Doctors also site current research (1,2,3) which shows that not all cases of schizophrenia become worse after using Cannabis. It is also now being considered that vulnerability to the side effects of cannabis comes from a genetic predisposition.
The take home message is that the main ingredient of cannabis may become an effective treatment for patients with a severe mental illness. And that the Endocannabinoid system might be more important and complex than previously thought.
Posted in Cannabination, Contributing Author: Jahan Marcu | 1 Comment »
Tuesday, July 21st, 2009
The Journal of Neuroendocrinology published a review last year, which suggests that oral THC may significantly reduce plaque development in diseases associated with obesity, such as atherosclerosis.
Atherosclerosis, a condition of plaque deposits in the lining of the arteries that results from a diet high in cholesterol, is one of the major causes of death in overweight/obesity-related disease. The plaque is created as a by-product of specific cells, called macrophages, when they consume fatty particles. As the plaque gathers, the walls of arteries become stiff and eventually collapse.
The study suggests that THC interacts directly with macrophages and suppresses their plaque-creating abilities through the Cannabinoid Type II receptor (CB2R). Immune cells in our body, such as macrophages, have many more cannabinoid receptors expressed on their surface – this makes them an exceptionally strong target for cannabis-based medicines.
The authors note that oral administration of low doses of THC resulted in significant inhibition of plaque development, an effect that could be reversed by blocking the CB2R.
What does this mean for humans? It is difficult to say without further research. But the results are hopeful. Given the politics surrounding cannabis, it might be a long while before the FDA approves a study in humans on cannabis and atherosclerosis. On the other hand, research such as this shows not only that we have only begun to investigate the healing potential of this remarkable natural compound, but the importance of advocating for a more open environment for future research.
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