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What Drugs Impact The Brain’s Cannabinoid Receptors

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Why Do Different Doses Of Thc Have Different Results

Scythian CEO on the potential impact of cannabinoid drugs on traumatic brain injuries

As you might have guessed by now, there is a brain centre for anxiety. The amygdala regulates fear and other emotional responses.

Remember glutamate and GABA, the green and red stoplights of our neural activity?

The current theory is that a low dose of THC will inhibit the release of glutamate in the amygdala. GABA builds up, calming activity.

A high dose of THC will inhibit GABA neurons. Glutamate builds up, activating the amygdala.

The glutamate/GABA balance is thought to be the switch that flips between a pot experience that is pleasant and unpleasant.

But these theories are based on animal research. Study of human subjects may lead to new theories.

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Lsd Pcp Ketamine And Hallucinogens

A class of drugs that leads to distortions of reality and perceptions, hallucinogens are typically broken down into two main categories: classic hallucinogens and dissociative drugs , per NIDA. It is not certain exactly how these drugs work in the brain however, it is largely understood that they interrupt normal communication between neurotransmitters. Dissociative drugs are believed to disrupt the action of glutamate, a brain chemical that is involved with memories, cognition, emotions, and how people perceive pain. PCP interacts with dopamine as well, while salvia activates the kappa opioid receptor present on nerve cells, per NIDA. Dissociative drugs can make people feel separate from themselves, their environment, and reality. This can result in impaired motor functions, auditory and visual distortions, memory loss, anxiety, numbness, and body tremors.

Prevalence Of Cannabis Use

The prevalence of cannabis use has increased markedly over the past decade in young people in the UK, although patterns of consumption vary between different social groups. A survey of 3075 university students from 10 UK universities found that about 60% had some experience with cannabis nearly 25% had tried it more than once or twice and 20% of students reported regular use . Experience with cannabis had usually started at school, and other surveys have shown that 30-40% of 15- to 16-year-olds have tried it .

Among 785 second-year medical students from seven UK medical schools surveyed in 1996, 46% reported cannabis use and 10% were taking it at least once a week . A survey of 90 house officers found that nearly 30% reported current cannabis use and 11% used it weekly or monthly .

These users are fairly moderate compared with some others. Some users report daily cannabis use, smoking up to 15 or more joints daily. Many of these are unemployed youths who smoke to obtain a high level of intoxication and may be exposed to several hundreds of milligrams of THC daily. Other groups with a high prevalence of cannabis use are alcohol and polydrug misusers and psychiatric patients.

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Disrupting Endocannabinoid Signaling Decreases Drug

Endocannabinoids are necessary for drug-induced increases in tonic and phasic dopamine release. Endocannabinoids are required for ethanol-induced increases in tonic dopamine concentrations in the nucleus accumbens. When administered independently, ethanol increased dopamine concentrations. When coadministered with rimonabant , ethanol failed to increase accumbal dopamine concentrations. Disrupting endocannabinoid signaling with rimonabant reversed ethanol-induced increases in the neural activity of an antidromically identified ventral tegmental area dopamine neuron. Endocannabinoids are required for drug-induced phasic dopamine events. Cocaine significantly increased transient increases in nucleus accumbens dopamine concentration. Rimonabant coadministration significantly attenuated the cocaine-induced increases in phasic dopamine release. Vehicle alone failed to alter phasic dopamine events .

So More Thc Means More Dopamine

How Cannabinoids Affect the Brain

Only to a point. The brain is a self-tuning instrument that always seeks balance.

If excessive dopamine levels continue, dopamine receptors in the brain may temporarily close off.

This could explain why heavy cannabis users experience less reward from pleasurable things when they arenât high.

They may find themselves smoking more pot to get the same high, and enjoying themselves less when they are sober.

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How Cannabinoid Receptors Work

The best way to imagine cannabinoids and their receptors is like a lock and key. When a person consumes cannabis, the cannabinoids THC and CBD flood your body in search of receptors .

When they find one that fits, the effects of the cannabinoid and the function and location of the receptor click together and messages are sent through the rest of your body.

As an example: Taking a dose of CBD oil can inhibit your appetite, whereas a THC-rich strain can increase appetite because it binds more readily with the CB1 receptor. Hence why you get munchies from certain strains of cannabis, but not from others.

However, the ECS is unique in that it communicates backward: this particular sort of cell-to-cell communication inhibits the immune response, reduces inflammation, relaxes muscles, lowers blood pressure, and normalizes stimulated nerves. Basically, our natural endocannabinoids check to make sure not too much is happening in your body before accepting more stimulation or the system creating more messages.

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What this means is that endocannabinoids are created on demand and can act as a dimmer switch that affect how quickly, often, and where messages get transmitted.

How does it do this?

Interactions Of The Opioid And Cannabinoid Systems In Reward: Insights From Knockout Studies

  • CNRS, Laboratoire de Neurosciences Cognitives et Adaptatives UMR7364, Faculté de Psychologie, Neuropôle de Strasbourg Université de Strasbourg, Strasbourg, France

The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides . The endogenous cannabinoid system comprises lipid neuromodulators , enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2. These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction. Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry. Extending classical pharmacology, research using genetically modified mice has provided important progress in the identification of the specific contribution of each component of these endogenous systems in vivo on reward process. This review will summarize available genetic tools and our present knowledge on the consequences of gene knockout on reinforced behaviors in both systems, with a focus on their potential interactions. A better understanding of opioidcannabinoid interactions may provide novel strategies for therapies in addicted individuals.

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Does Thc Affect Mental Function

Pot users have long been stereotyped as having reduced mental abilities. When cannabis was illegal, it was difficult to study the effect of THC on a large number of human subjects, but several effects have been proven.

Coordination, reaction time, concentration and decision-making abilities are all affected by THC.

Mood-altering drugs can be dangerous for people with a personal or family history of schizophrenia or bipolar disorder.

Studies on humans show that THC intoxication causes a measurable difficulty in accessing verbal memories.

When they are high, pot users may be unable to find the word they want to express a certain thought.

Studies link this outcome to the presence of THC in the brain. Once the THC breaks down, that tongue-tied state passes.

The larger question is whether THC use results in the impairment of cognitive performance after the intoxication wears off.

Now that pot is legal, better studies are planned to answer that question.

Cannabinoids As Antiemetic Agents

What Does Cannabis Do To The Brain? | Brit Lab

The ability of THC and the synthetic cannabinoid nabilone to control the nausea and vomiting associated with cancer chemotherapy is one of the few well documented medical applications for these drugs . THC and nabilone were approved for medical use in the USA, although neither drug has found much utility. The narrow window between the antiemetic dose and that causing unwanted psychic effects made these drugs difficult to use. The advent of serotonin 5HT3 receptor antagonists as new and more powerful antiemetic drugs that were free of unwanted psychic effects during the 1980s also made the cannabinoids less attractive.

Studies in experimental animals have confirmed that the antiemetic effects of cannabinoids are mediated through CB1 receptors , and in some susceptible species the CB1 antagonist rimonabant is emetic, an effect that can be blocked by THC or WIN55,2122 .

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Composition And Composition Changes Of Cannabis/marijuana Preparations

Over the last 2030 years, the composition of cannabis products has changed due to the fact that cannabis is grown in doors and that strains are cultivated with different THC and CBD contents and THC:CBD ratios . Thus, it was found in a large European study in samples from 28 EU countries and Norway and Turkey that from 2006 until 2016 the THC content in resin and in herbal cannabis increased from 8.14 to 17.22% and from 5.0 to 10.22%, respectively . A similar development was found in samples from France over a 25-year period ranging from 1992 to 2015 . Comparable increases in THC content in the resin were found in Denmark from 2000 to 2017 with an increase in THC:CBD ratio from 1.4 in 2008 to 4.4 in 2017 .

Table 1.

Changes in the composition of marijuana and hashish

Interestingly, in the Netherlands the THC content remained nearly unaltered . However, that means that in the Netherlands the THC resin content in 2005 was with 16% in the range, which was achieved in other European countries at 2016.

What Drugs Impact The Brains Cannabinoid Receptors

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Synthetic Marijuanas Effect On The Brain

Synthetic Marijuana, a man-made Hallucinogenic substance typically sprayed onto plant material, is not safe for human consumption but has become popular in recent years. Also known as Fake Weed, it produces mind-altering effects and can cause the individual to act in an odd manner. Synthetic Marijuana is illegal and may have toxic ingredients that can cause increased heart rate, unexplained bleeding, and vomiting.

Similarly to Marijuana, Synthetic Marijuana affects the brain by attaching itself to the Cannabinoid receptor type 1 found in both the central and peripheral nervous systems. Synthetic Weed binds more strongly to CB1 receptors than THC, making it at least 100 times more potent in the brain. Because CB1 receptors have multiple locations in the brain, side effects can be intense and harmful.

Synthetic Marijuana may cause the brain and body to experience:

  • Memory loss

Types Of Cannabinoid Receptors

Can You Overdose or Die From Consuming Cannabis?

Dont get us wrong, cannabis can and does interact with cannabinoid receptors but the receptors werent created for cannabis. They were created as part of the ECS to receive endocannabinoids from your brain. Interestingly enough, these receptors also far outnumber any other receptor found in the brain.

Technically, the ECS is just being supplemented when a person consumes cannabis and their receptors are stimulated. Thankfully, this means that many deficiencies and overexpression of certain characteristics of the disease can be course-corrected by plant-based cannabinoids like THC and CBD.

As we mentioned, there are 2 main types of receptors: CB1 and CB2.

Cannabinoid Receptor 1 receptors are mainly located in the brain and nervous system, as well as in the lungs, liver, and kidneys. Our natural endocannabinoids and the cannabinoid THC from cannabis mainly bind with CB1 . This gives patients relief from pain, nausea, and depression, among other things.

Cannabinoid Receptor 2 receptors are found mainly in the immune system, with a heavy concentration in the spleen and in the gastrointestinal system. CB2 receptors which bind best with the endocannabinoid 2-AG and cannabis CBD are involved in the regulation of appetite, immune system functions like inflammation and pain management.

Scientists are on the cusp of determining a third type of cannabinoid receptor , but research in this area is ongoing and inconclusive as of now.

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Mopr Agonists Enhance Daergic Activity

Interestingly, behavioral evidence suggests that opioids can exert rewarding/reinforcing effects independent of DA function. For example, found that systemic DA antagonism with low doses of the DA receptor antagonist alpha-flupenthixol enhanced cocaine self-administration, but did not affect self-administration of heroin, while high doses abolished self-administration of cocaine, but not heroin . Furthermore, DA-deficient mice still acquire CPP for morphine , although at higher doses than those employed in other studies. While the mechanisms underlying DA-independent opioid reward remain unclear, showed that intra-NAc DA receptor antagonism blocked morphine CPP in dependent, but not naive, rats. This suggests that opioid reward may shift between DA-dependent and DA-independent mechanisms conditional to an organisms motivational state. However, the neural underpinnings of this phenomenon remain unknown.

Beyond Thc And Cbd: The Science Of Cannabinoids And The Brain

There are more than 100 cannabinoids in cannabis, and all of them can affect our brains and bodies. Here’s what science does â and doesn’t â know about cannabinoids and the brain.

When we think cannabis, most of us think of the chemical THC â although CBD is quickly rising in popularity, too. Both cannabidiol and tetrahydrocannabinol, to give them their full names, are cannabinoids â chemical compounds found in marijuana. But while they are the most famous, they are far from the only cannabinoids.

In fact, scientists have discovered more than 100 other cannabinoids â and those are just the ones found in the cannabis plant. In total, there are more than 500 cannabinoids, all of which can have an affect on our bodies and brains. What is perhaps most exciting about these myriad chemicals are the potential therapeutic effects they could have â if the research holds up, cannabinoids could represent hundreds of new drugs for human benefit.

And that list is growing.

In a December 2019 study, scientists announced the discovery of two new cannabinoids â and both of them could pack some real psychoactive power, even compared to the well-known THC.

“All cannabinoids are equally important.”

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Exogenous Cannabinoids And Their Receptors

The principal active component in the complex mixture of cannabinoids present in extracts of the plant Cannabis sativa is 9tetrahydrocannabinol . THC is a sticky resin that is not soluble in water. Smoking remains the most efficient means of delivering the drug and experienced users can titrate the dose by adjusting the frequency and depth of inhalation . THC or cannabis extracts can also be taken orally in fatcontaining foods or dissolved in a suitable pharmaceutical oil, but absorption is delayed and variable . A series of manmade synthetic cannabinoids, some of which are more potent and more water soluble than THC, is also available . All of these compounds act as agonists at the CB1 cannabinoid receptor , which is the only one known to be expressed in the brain. A second cannabinoid receptor, CB2, is expressed only in peripheral tissues, principally in the immune system . THC and the synthetic cannabinoids also act to some extent as agonists at the CB2 receptor. Both cannabinoid receptors are members of the Gprotein coupled class, and their activation is linked to inhibition of adenylate cyclase activity . A series of synthetic drugs is also now available that act as specific antagonists at CB1 or CB2 receptors . One of these compounds, rimonabant, which acts selectively to block CB1 receptors , has been widely used in studies of the actions of cannabinoids in the CNS .

Cannabinoids Increase Tonic Dopamine Levels

2-Minute Neuroscience: THC

Cannabinoids increase tonic and phasic dopamine release. The cannabinoid CB1 receptor agonist WIN55,212-2 increased tonic dopamine concentrations in the shell region of the nucleus accumbens in comparison to vehicle . The cannabinoid CB1 receptor antagonist rimonabant prevented the WIN-induced increase in accumbal dopamine concentration. WIN55,212-2 dose-dependently increased the neural activity of an antidromically identified ventral tegmental area dopamine neuron. Rimonabant reversed the WIN-induced increase in dopamine neural activity. WIN55,212-2 increased the frequency of phasic dopamine events detected in the shell region of the nucleus accumbens in comparison to pre-treatment values. To assess for cannabinoid-induced changes in dopamine uptake, dopamine release was evoked by electrical stimulation applied to the medial forebrain bundle. WIN55,212-2 failed to increase the width of electrically evoked dopamine events, suggesting that cannabinoids do not increase nucleus accumbens dopamine by decreasing dopamine uptake. 9-Tetrahydrocannabinol and WIN55,212-2 increased phasic dopamine neural activity. Both cannabinoids increased the number of bursting events observed and the number of impulses occurring per burst. A significant difference versus pre-drug levels.

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Cannabinoid Mechanisms In The Hippocampus And Effects On Memory

One of the well established effects of acute intoxication with cannabis in man is an impairment of shortterm memory . Many studies have shown significant effects on shortterm memory, particularly when tests were used that depend heavily on attention . Animal studies have also found that THC, synthetic cannabinoids and anandamide cause deficits in shortterm memory in spatial learning tasks . These include delayed matching or nonmatching tests in rodents , performance in a radial arm maze , and a fixed ratio food acquisition task in squirrel monkeys . The effects of both cannabinoids and anandamide were reversed by rimonabant, indicating that they are mediated by the CB1 receptor.

One approach to answering the question of what role the tonic release of endocannabinoids may play in hippocampal function has been to examine the effects of CB1 receptor knockout or of selective CB1 receptor antagonists. Un fortunately, these studies have so far yielded conflicting results. reported a significant enhancement of LTP in CB1 knockout mice, and found a significant enhancement of memory in such animals. However, tests with the CB1 antagonist rimonabant showed no effects on LTP or on learning and memory in a spatial learning task , although

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