cb2 receptors

Natural chemical helps brain adapt to stress

A natural signaling molecule that activates cannabinoid receptors in the brain plays a critical role in stress-resilience — the ability to adapt to repeated and acute exposures to traumatic stress, according to researchers at Vanderbilt University Medical Center.

The findings in a mouse model could have broad implications for the potential treatment and prevention of mood and anxiety disorders, including major depression and post-traumatic stress disorder (PTSD), they reported in the journal Nature Communications.

“The study suggests that deficiencies in natural cannabinoids could result in a predisposition to developing PTSD and depression,” said Sachin Patel, M.D., Ph.D., director of the Division of Addiction Psychiatry and the paper’s corresponding author.

“Boosting this signaling system could represent a new treatment approach for these stress-linked disorders,” he said.

Patel, the James G. Blakemore Professor of Psychiatry, received a Presidential Early Career Award for Scientists and Engineers last year for his pioneering studies of the endocannabinoid family of signaling molecules that activate the CB1 and CB2 cannabinoid receptors in the brain.

Tetrahydrocannabinol (THC), the active compound in marijuana, binds the CB1 receptor, which may explain why relief of tension and anxiety is the most common reason cited by people who use marijuana chronically.

Patel and his colleagues previously have found CB1 receptors in the amygdala, a key emotional hub in the brain involved in regulating anxiety and the fight-or-flight response. They also showed in animal models that anxiety increases when the CB1 receptor is blocked by a drug or its gene is deleted.

More recently they reported anxiety-like and depressive behaviors in genetically modified mice that had an impaired ability to produce 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid. When the supply of 2-AG was increased by blocking an enzyme that normally breaks it down, the behaviors were reversed.

In the current study, the researchers tested the effects of increasing or depleting the supply of 2-AG in the amygdala in two populations of mice: one previously determined to be susceptible to the adverse consequences of acute stress, and the other which exhibited stress-resilience.

Augmenting the 2-AG supply increased the proportion of stress-resilient mice overall and promoted resilience in mice that were previously susceptible to stress, whereas depleting 2-AG rendered previously stress-resilient mice susceptible to developing anxiety-like behaviors after exposure to acute stress.

Taken together, these results suggest that 2-AG signaling through the CB1 receptor in the amygdala promotes resilience to the adverse effects of acute traumatic stress exposure, and support previous findings in animal models and humans suggesting that 2-AG deficiency could contribute to development of stress-related psychiatric disorders.

Marijuana use is highly cited by patients with PTSD as a way to control symptoms. Similarly, the Vanderbilt researchers found that THC promoted stress-resilience in previously susceptible mice.

However, marijuana use in psychiatric disorders has obvious drawbacks including possible addiction and cognitive side effects, among others. The Vanderbilt study suggests that increasing production of natural cannabinoids may be an alternative strategy to harness the therapeutic potential of this signaling system.

If further research finds that some people with stress-related mood and anxiety disorders have low levels of 2-AG, replenishing the supply of this endocannabinoid could represent a novel treatment approach and might enable some of them to stop using marijuana, the researchers concluded.

Just Follow Your Nose


HAVE YOU EVER wondered why cannabis varieties smell very different? this difference is due to the presence of different volatile essential oils called terpenoids. in cannabis, terpenoids are primarily produced in the flowers and leaves, especially in the trichomes.

anytime you smell cannabis or virtually any fruit, herb, tree, flower or plant, you smell its terpenoids. all spices and herbs derive their unique aromas and tastes from terpenoids.  terpenoids are the basis of most natural fragrance’s, flavoring’s and coloring’s.

terpenoids are the biggest family of natural plant chemicals, with over 30,000 produced in nature. they’re found in all organisms. chlorophyll, beta-carotene, and vitamin E are examples of well-known terpenoids found in plants.

there are over 120 (some say 200) different terpenoids in cannabis, but only a dozen or so are found in enough quantity to significantly modify a cannabis strain’s effects. terpenoids interact with the different cannabinoids and modify THC’s effect, which is why different varieties of cannabis with similar smells often have similar effects.


(the following information concerning specific terpenoids in cannabis was taken from Cannabis Heath News Magazine)

THE MAJOR TERPENES OF CANNABIS RESIN AND THEIR EFFECTS:

BORNEOL – BORNEOL IS A MAJOR COMPONENT OF CANNABIS RESIN THAT CAN ALSO BE FOUND IN CINNAMON AND WORMWOOD (ARTEMESIA SPP). IN CHINESE MEDICINE HERBS CONTAINING BORNEOL ARE RECOMMENDED FOR FATIGUE AND OVERSTRESS. BORNEAL IS MENTIONED TO BE A CALMING SEDATIVE.

CORRYPHYLLENE – CORRYPHYLLENE IS A MAJOR COMPONENT OF CANNABIS RESIN THAT CAN ALSO BE FOUND IN BLACK PEPPER AND CLOVES. IT IS A FAIRLY WEAK AGONIST OF THE TYPE 2 CANNABINOID RECEPTORS (CB2). AS A CONSTITUENT OF A SALVE OR LOTION CORPHYLLENE IS AN EFFECTIVE ANTI- INFLAMMATORY AND ANALGESIC. DRUG DOGS ARE TRAINED TO SPECIFICALLY SNIFF OUT CORPHYLLENE EPOXIDE, A SIMILAR COMPOUND PRODUCED ONLY BY CANNABIS.

CINEOLE/EUCALYPTOL – CINEOLE/EUCALYPTOL CONTENT IS QUITE VARIABLE ACROSS VARIETIES OF CANNABIS, BUT IS OFTEN A MAJOR COMPONENT OF THE ESSENTIAL OIL. IT IS ALSO FOUND IN ROSEMARY AND EUCALYPTUS AND IS USED TO INCREASE CIRCULATION, AND REDUCE PAIN AND SWELLING WHEN APPLIED TOPICALLY. IT READILY CROSSES THE BLOOD/BRAIN BARRIER, POSSIBLY HELPING CANNABINOIDS TO CROSS MORE READILY AS WELL. THE EFFECTS OF CINEOLE, WHEN COMBINED WITH ORAL OR SMOKED CANNABIS, ARE REPORTED AS BEING VERY UPLIFTING, NOTICEABLY INCREASING MENTAL AND PHYSICAL ENERGY. THIS TERPENE, OR OTHERS LIKE IT, MAY BE RESPONSIBLE FOR THE REPORTED DIFFERENCE IN EFFECT BETWEEN INDICA AND SATIVA STRAINS WITH A SIMILAR CANNABINOID PROFILE.

LIMONENE – FOUND IN CANNABIS RESIN AS WELL AS LEMON RINDS, LIMONENE IS AN ANTI-BACTERIAL, ANTI FUNGAL AND ANTI CANCER AGENT. IT SMELLS SURPRISINGLY LIKE ORANGES OR TROPICAL FRUIT.  CURRENTLY UNDERGOING TRIALS FOR USE AS AN ANTI DEPRESSANT, IT IS ALSO KNOWN TO INCREASE THE ABSORPTION OF OTHER TERPENES BY MAKING CELL MEMBRANES MORE PERMEABLE. THE PRESENCE OF THIS ANTI FUNGAL AGENT MAY BE HELPFUL IN PROTECTING AGAINST ASPERGILLUS INFECTION IN THOSE WITH COMPROMISED IMMUNITY WHEN USING SPOILED OR POORLY CURED MARIJUANA. LIMONENE IS CURRENTLY IN TRIALS TO STUDY ITS ABILITY TO PREVENT BREAST CANCER FORMATION.

(*DELTA-3-CARENE – A COMPONENT OF CANNABIS, ROSEMARY, PINE, AND CEDAR RESIN.  ~~~~~ AROMATHERAPY OILS THAT CONTAIN HIGH LEVELS OF DELTA-3-CARENE ARE USED TO DRY EXCESS FLUIDS FROM THE EYES, NOSE, OR MOUTH. IT IS THOUGHT TO BE AT LEAST PARTIALLY RESPONSIBLE FOR THE DRY MOUTH AND EYE PROBLEMS THAT ARE COMMON SIDE EFFECTS OF THE USE OF CANNABIS.*)

LINALOOL – THIS MAJOR COMPONENT OF CANNABIS AND LAVENDER OILS IS BELIEVED TO POSSESS ANTI ANXIETY AND SEDATIVE PROPERTIES. STRAINS THAT ARE HIGH IN LINALOOL AND SIMILAR COMPOUNDS MAY BE PARTICULARLY BENEFICIAL FOR PATIENTS WHO EXPERIENCE INSOMNIA WHEN CONSUMING CANNABIS.

MYRCENE – SIGNIFICANT CONCENTRATIONS OF MYRCENE ARE PRESENT IN CANNABIS RESIN. IT IS ALSO FOUND IN MANGO, HOPS, LEMON GRASS, EAST INDIAN BAY TREE, AND VERBENA. BECAUSE OF ITS APPEALING FRAGRANCE, MYRCENE IS USED IN THE PERFUME INDUSTRY. IT HAS A SIMILAR MODULATING EFFECT ON THE BINDING OF CANNABINOID AGONIST DRUGS AS CANNABIDIOL, POSSIBLY REDUCING EFFECTS OF CANNABIS RESIN THAT ARE FOUND TO BE UNPLEASANT FOR SOME MEDICAL USERS. IT HAS ANTI MICROBIAL, ANTI SEPTIC, ANALGESIC, ANTI OXIDANT, ANTI CARCINOGEN AND ANTI-INFLAMMATORY PROPERTIES. IT HAS SHOWN SOME PROMISE WHEN USED AS AN ANTI DEPRESSANT, OR AS AN ADDITIVE TO OTHER ANTI DEPRESSANT DRUGS AND IS ALSO USED IN MASSAGE THERAPY AS A MUSCLE RELAXER.



TERPINEOL – MINOR COMPONENT OF CANNABIS RESIN, USED EXTENSIVELY IN THE PERFUME INDUSTRY. INTERESTINGLY THIS TERPENE DECREASES MOTILITY OF LAB RATS BY 45 PERCENT, THIS OBSERVATION COUPLED WITH THE FACT THAT THIS IS A TERPENE PRODUCED PRIMARILY IN CANNABIS INDICA PLANTS INDICATES TERPINEOL COULD PLAY A ROLE IN DECREASED MOTILITY SOMETIMES REFERRED TO AS “COUCH LOCK”.



so, the next time you are confused by all the new strain names, just check the chart above, use your nose, and you can easily figure out which one is right for you.  - CW

The moment you’ve been waiting for... Marijuana!

Should it be legalized? Eh. Probably, I don’t see why not. But that’s not what we’re here for!

So as far as edibles vs. smoking goes, the action of smoking is WAY faster because it goes straight to the lungs and absorbed directly into the blood stream. Though it’s not talked about as much, marijuana does have some kind of “tar” although it’s carcinogenic tendancies aren’t really as well known. When you consume marijuana (edibles, brownies), the effects stick around longer, but it’s also slower, and the actually amount of marijuana you get into your system will depend on how much food you’ve had, how hydrated you are, sex, weight, age, etc. It also has to endure metabolism of the liver BEFORE it gets to the site of activity, in addition to the metabolism it’ll have to deal with AFTER use.

THC, the active compound in marijuana, is aborbed readily through the lungs, BUT EVEN FUNNER, a Whole 2/3 of it is excreted in the FECES! That’s the most we’ve seen so far. Also a new trait, it’s so fat soluble, that it actually gets put into fatstores. It takes about 2 weeks in total to remove MOST evidence of marijuana from your system… but even then it’s hard to know for sure…

There are 4 stages to marijuana

Buzz: this is the euphoria felt at the very beginning of use when you just feel the effects taking in and you reach the

High: still euphoria, disinhibition, and laughter. Everything seems funny, and everything is alright. Very low stress… although the peak of low stress occurs when you’re

Stoned: a relaxed and dreamlike state, when this ends, you finally begin to

Come-down: where you return to your sense and reality

In addition to these behavioral effects, you also feel warm, from an increased blood flow, and heart rate, and of course THE MUNCHIES Which are totally real.

There are also long-term effects on cognition… that might be an issue :/

Cannibus gets its very own receptor. Because the only reason we learned about these receptors was from studying this drug! Thanks weed! CB1 receptors are located in the base of the brain, hippocampus, and cortex, basically meaning it affects memory, thought, and movement, which it does! It is located on the axon terminal of the presynaptic cell, meaning it is more of a modulating receptor. When cannabinoids bind to these receptors, it likely prevents action of other neurotransmitters from being released. CB2 receptors are primarily located in the immune system, fat, Gastrointestinal tract (GI), and microglia, but there’s also evidence that it’s also in the central nervous system… so… it’s everywhere. So that explains some of its peripheral actions (i.e. the GI tract and the munchies)

Now, THC derived from marijuana isn’t available in our brains… so why do we have receptors for it. It’s not like other drugs we’ve learned about that just act on already known neurotransmitters… it has its own set of endocannabinoids, which are cannabinoids produced by the brain. Two known endocannabinoids are Anandamide and 2-AG, although evidence indicates that 2-AG is the true endocannabinoid.

So there’s weed for ya.