Professor of Pot – Weed News Marijuana News, Policy, Culture and Law Thu, 21 May 2020 17:53:05 +0000 en-US hourly 1 https://wordpress.org/?v=6.0.11 Do Cannabis Terpenes Have Sedative or Anxiolytic Effects? /do-cannabis-terpenes-have-sedative-or-anxiolytic-effects/ /do-cannabis-terpenes-have-sedative-or-anxiolytic-effects/#respond Wed, 02 Aug 2017 14:26:56 +0000 http://www.weednews.co/do-cannabis-terpenes-have-sedative-or-anxiolytic-effects/

Can the terpenes in cannabis really have relaxing or anti-anxiety effects? What happens when they are combined with THC? Every cannabis site loves to talk about the “health benefits” of terpenes. Many cannabis terpenes are promoted as having calming, sleep-promoting, anti-stress, anti-anxiety effects. When I hear these descriptions, it sounds to me like they are […]

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Can the terpenes in cannabis really have relaxing or anti-anxiety effects? What happens when they are combined with THC?

Every cannabis site loves to talk about the “health benefits” of terpenes. Many cannabis terpenes are promoted as having calming, sleep-promoting, anti-stress, anti-anxiety effects. When I hear these descriptions, it sounds to me like they are sedatives.

Unfortunately there is often little detail on the science behind these claims. In fact, it was difficult to even find a proper review on sedative effects of terpenes in the scientific literature. So I made this guide on the sedative and anxiolytic (anti-anxiety) effects of terpenes to understand the science behind what they do and how they work.

Note that I am not including studies on the effects of terpenes tested as aromatherapy. There is some interesting research in this area, but I will cover this in a separate article. This article will focus on the effects of terpenes taken internally.

I will focus primarily on animal and mechanistic studies. The reason? There is actually very little research on isolated terpenes in humans. However, I will be covering what research is available in a future article.

What Are The Properties of Sedatives?

We need to be a little more specific when we say that a terpene has sedative or calming effects. Not every sedative is exactly the same, but many share some basic properties that I will describe below.

Reduced physical activity: This is the most classic sedative effect, akin to the “couch-lock” described for some cannabis strains.

Hypnotic: This is the ability to induce sleep. Sedatives may both reduce the time to fall asleep as well as induce a longer period of sleep.

Anxiolytic: Many sedatives will reduce anxiety.

Anticonvulsant: Due to inhibiting neuronal activity, sedatives can reduce the frequency or intensity of seizures.

Motor coordination: Sedatives typically impair coordination. Hence you will see this warning on pharmaceutical sedatives: “Do not drive or operate heavy machinery”.

Which Cannabis Terpenes Are Reported To Have Sedative Effects?

The terpenes in cannabis are found in the essential oils of many other plants. Many of these plants have had traditional medicinal uses for hundreds of years. Some of these traditional medicinal uses include calming or sleep-inducing effects (basically the things that a sedative would be used for). Here is a list of terpenes that traditional use or modern research indicates have sedative or anxiolytic effects:

Beta-Caryophyllene
Limonene
Linalool
Myrcene
Alpha-Pinene
Phytol
α-ձ辱ԱDZ
Terpinolene

Note: This list is not exhaustive, but I believe it contains the most important ones. I will explore in the sections below whether there is any evidence to support the claims that these terpenes have sedative properties.

sedative effects of terpenes

Myrcene,α-Pinene, Phytol, Terpinolene, and α-ձ辱ԱDZ

I am lumping 5 of the terpenes together, because they seem to act in the same way. All have similar activities in rodents and all have a similar mechanism of action by working through the GABA system.

Sedative Activity of GABAergic Terpenes in Animals

Myrcene had a variety of  in rodents (100-200 mg/kg i.p.). It suppressed locomotor activity,induced sleep, and reduced motor coordination in the rotarod test, although it did not show anxiolytic effects. Another study showed that myrcene (200 mg/kg i.p.) .

α-ʾԱԱ (0.2-0.4 mg/kg i.p.). Another study showed an  time (100 mg/kg oral). α-辱ԱԱ did , although only doses up to 0.17 mg/kg were tested. Inhalation of α-辱ԱԱ (which produced measurable concentrations in the brain) produced an , although higher brain concentrations were associated with an excitatory effect. I did not find any studies that looked directly at the anticonvulsant activity of α-辱ԱԱ, but several essential oils that have α-辱ԱԱ as a component reduced seizures.

Phytol has shown numerous  in rodents. It showed sedative effects in the open field test (25-75 mg/kg i.p.), increased sleep time (25-75 mg/kg i.p.), had anxiolytic effects (75 mg/kg i.p.), and impaired motor coordination (75 mg/kg i.p). Another study showed that phytol has  (25-75 mg/kg i.p.)

Terpinolene (0.01-0.1 mg/kg i.p.) significantly . Other sedative activities of terpinolene have not been tested.

Mechanism of GABAergic Terpenes Sedative Activity

GABA is the main inhibitory neurotransmitter in the brain and it exerts its effects through reducing neuronal excitability. There are two receptors for GABA – the GABAreceptor (an ion channel) and the GABAB receptor (a G protein-coupled receptor).

A class of sedatives called benzodiazepines work through the GABAreceptors. They can bind to a distinct receptor site and act as positive allosteric modulators of GABA. In other words, they can increase activation of the receptor by GABA.

GABA.linonene,terpenes,sedative

There is a variety of evidence that the terpenes described above exert their effect through the same benzodiazepine binding site of GABAreceptors . For one, the pharmacologic profile of these terpenes is similar to that of benzodiazepines. Flumazenil, which is an antagonist of the benzodiazepine binding site, blocks the effects of these terpenes in vitro and in vivo.

Myrcene and α-辱ԱԱ  in cell experiments. The effect of α-辱ԱԱ in neurons was . In rodents, flumazenil blocked the sedative effects of  (which has high myrcene content),, and .

α-terpineol can also  activity in cells. Even though its pharmacology in rodents has not been characterized, we can assume that it will be similar to the other GABAergic terpenes.

Phytol may have an additional GABA-related mechanism through , which is is the enzyme that breaks down GABA. Thus, it may be able to raise GABA levels in the brain in addition to increasing activation of the GABAreceptor.

Possible Synergy of GABAergic Terpenes with Cannabinoids

GABAstimulating drugs (like the benzodiazepine flurazepam)  of THC in mice. Catalepsy is the decreased ability to initiate movement. This enhancement of THC’s cataleptic effects occurred at a dose of flurazepam so low that it did nothing by itself. Although THC’s cataleptic effects are distinct from sedative effects (and are also much more subtle in humans than rodents), this may contribute to the couch-lock effect.

Another study indicated that chronic (but not acute) cannabis treatment in mice actually  for their binding site. Since the GABAergic terpenes bind to this same site as benzodiazepines, it is possible that the anxiolytic effects of low doses of terpenes may be greater in chronic cannabis users.

 in regular cannabis users did not significantly impact subject’s self-rated high. They did feel more sedated after the THC/diazepam combination, but this effect was more additive than synergistic at the diazepam doses tested. This does not negate the possibility that there is synergistic activity with lower doses of terpenes.

Linonene,terpene,sedative

Limonene

Sedative Activity of Limonene in Animals

Limonene has shown most of the classic sedative effects in animal studies.  in rodents found that limonene reduced locomotor activity (100-200 mg/kg i.p.), induced sleep (200 mg/kg i.p.), and impaired motor coordination (50 mg/kg i.p.). However, it did not show anxiolytic effects in the elevated plus maze test. Limonene was also an  (200 mg/kg i.p.).

ճ of limonene have also been tested. Limonene (0.84 mg/kg i.p.) significantly reduced serum corticosterone levels (a stress hormone) elevated by physical or social stress. It also reversed many of the changes in in brain monoamine neurotransmitters induced by these stressors, including dopamine, norepinephrine, and serotonin.

 looked at chronic dosing with d-limonene (one of the two limonene enantiomers). After 1 week of limonene dosing, brain glutamate levels were decreased and brain GABA levels were increased (both at 25-50 mg/kg i.p.). There were minimal changes in brain monoamine neurotransmitters and serum corticosterone in the absence of any stressor. However, limonene did partially block stress-induced increases in serum corticosterone.

Mechanism of Limonene Sedative Activity

The sedative mechanism of limonene may be multifaceted. On one hand, the decrease in brain glutamateԻincrease in brain GABmay be responsible for part of the sedative effect, although it is not clear whether this happens after single doses or only with chronic dosing.

Although limonene had , the GABAreceptor benzodiazepine binding site has a role in vivo. Some (but not all) of the changes in brain monoamine neurotransmitters from limonene were reversed by flumazenil. In a study of monoamine neurotransmitter release from rat brain slices, the limonene metabolites perillic acid and perillyl alcohol acted more strongly than limonene itself. These metabolites may have a benzodiazepine-like activity at the GABAreceptor which limonene itself lacks.

Finally, a Ի showed that limonene could directly bind to and activate the adenosine A2receptor. Caffeine, a known stimulant, is an antagonist of this receptor along with the other adenosine receptor subtypes. The adenosine A2receptor can regulate glutamate, GABA, and dopamine release, so this may be another mechanism through which limonene regulates neurotransmitter release.

Possible Synergy of Limonene with Cannabinoids

Since limonene (or rather its metabolites) increased GABAactivation, the same situation described above for the GABAergic terpenes may also apply to limonene.

In some cases, A2activation can increase the effects of cannabinoids and in some cases decrease the effects. Interestingly, the A2receptor  with the cannabinoid CB1 receptor. Complicating the matter further, CB1 activation results in indirect A2Aactivation. Also, THC and CBD are both .

Basically, interactions between the cannabinoid and adenosine systems are complex, making it difficult to speculate on synergy between THC and limonene.

cinnamon,linalool,terpenes,sedative

Linalool

Sedative Activity of Linalool in Animals

 in rodents showed that linalool decreased locomotor activity (175 mg/kg i.p.), but was not anxiolytic at 125 mg/kg i.p.  showed that linalool reduced locomotor activity (100-173 mg/kg i.p.), without a loss of motor coordination at 100 mg/kg. Linalool also  and had  (350 mg/kg i.p. and 2200-2500 mg/kg oral).

Two weeks of dosing with the two linalool enantiomers (500 mg/kg oral) revealed that both produced .

Mechanism of Linalool Sedative Activity

Linalool does not bind to the  or to the  of the GABAreceptor. Nonetheless, a 2014 study showed it could significantly augment GABAactivity in cells.

There is another mechanism of linalool that differentiates it from other terpenes. It can modulate the effects of glutamate, which is the main excitatory neurotransmitters in the brain. Glutamate can act through four different receptors.  (and other earlier studies) showed that linalool is an antagonist of the NMDA receptor,which is one of these glutamate receptors. Other NMDA receptors antagonists include dissociative anaesthetics such as ketamine, which have strong sedative activity.

Possible Synergy of Linalool with Cannabinoids

The hypothermic and reduced locomotor activity of THC itself are (at least partially) . There was a distinct  when a CB1 agonist was combined with an NMDA receptor antagonist (at a dose so low, it had no effect by itself). This highlights the possibility that there is also a synergistic sedative effect of low doses of linalool when combined with THC.

β-䲹DZԱ

Sedative Activity of β-caryophyllene in Animals

The sedative properties of β-caryophyllene were characterized in a ,, and  and were shown to be distinct from the GABAergic terpenes. In rodents,β-caryophyllene did not affect locomotor activity or motor coordination (doses up to 100 mg/kg i.p. and 200 mg/kg oral). However, it did mildly promote sleep (200-400 mg/kg oral), have anxiolytic activity (50 mg/kg i.p and 100-200 mg/kg oral), and have antiseizure activity (100 mg/kg i.p.).

Mechanism of β-caryophyllene Activity

β-caryophyllene is a cannabinoid CB2 receptor agonist, and has therefore been called a “dietary cannabinoid”.  The anti-anxiety effects from one  were completely blocked by a CB2 receptor antagonist, indicating that this is the sole mechanism of its anxiolytic effect. This was supported by , where anti-anxiety effects were not mediated through either the GABAAbenzodiazepine site or through the 5-HT1receptor. The lack of effect on locomotor activity and coordination further confirm that β-caryophyllene does not work through the GABA system. Therefore, at the right dose, it can be considered a non-sedating anxiolytic.

Possible Synergy of β-caryophyllene with Cannabinoids

Since THC is already a partial agonist of the CB2 receptor, I would expect little synergy between the two molecules. It is possible that there is a synergistic anti-anxiety effect between β-caryophyllene and CBD, since both exert their effects through different mechanisms. However, CBD is also a weak antagonist of the CB2 receptor and so high CBD doses may actually block the anxiolytic effects of β-caryophyllene.

Do Cannabis Terpenes Have Sedative or Anxiolytic Effects in Humans?

This is the million dollar question. Unfortunately I have run out of time and will have to address this in detail in a future article. In general, the evidence supporting these effects in humans is weak (but remember that absence of evidence is not evidence of absence).

Why did I bother to list all of the doses used in the animal studies above? The terpene doses required to see sedative effects in animals were generally very high…it would be near impossible to achieve equivalent doses through consumption of cannabis. While it is possible that a lower terpene dose is sufficient due to synergistic interactions with THC, this remains unproven in humans.

Another possibility is that terpenes exert some effects directly through their smell and not actual ingestion (i.e. aromatherapy). The jury is still out on this as well, but there have indeed been some studies that support it.

If you want to get future updates on this series on the entourage effect, please join the mailing list or follow me on Facebook!

Original article on Profofpot.com . syndicated by special permission.

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]]> /do-cannabis-terpenes-have-sedative-or-anxiolytic-effects/feed/ 0 Does CBD Block The High of THC in Cannabis? /does-cbd-block-the-high-of-thc-in-cannabis/ /does-cbd-block-the-high-of-thc-in-cannabis/#respond Fri, 21 Jul 2017 14:26:57 +0000 http://www.weednews.co/does-cbd-block-the-high-of-thc-in-cannabis/

CBD can reduce the activation of the cannabinoid CB1 receptor in cell experiments. Does this mean that it can actually prevent you from getting high? Cannabidiol (CBD) is the second most common cannabinoid after the more famous THC. Although CBD levels in most strains of cannabis are low (and have been dropping for decades), it […]

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CBD can reduce the activation of the cannabinoid CB1 receptor in cell experiments. Does this mean that it can actually prevent you from getting high?

Cannabidiol (CBD) is the second most common cannabinoid after the more famous THC. Although CBD levels in most strains of cannabis are low (and have been dropping for decades), it is currently gaining in popularity as a treatment for a number of conditions.

The high from cannabis is primarily from THC activating the CB1 receptor. In cells, CBD is able to block THC activation of the CB1 receptor. It logically follows then that CBD should block the psychoactive effects of THC (although also therapeutic effects of THC mediated by the CB1 receptor, such as the analgesic and anti-nausea effects).

With the surge in CBD popularity, there have been questions about whether taking CBD may block the high you get from THC. There are specific side effects of THC that CBD does block (anxiety, psychotic effects, and certain cognitive deficits). Those are important, and I will cover those in subsequent articles. However, I am covering just one thing here: can CBD reduce your high?

The CB1 Receptor Gets You High

The first thing to understand in this story is that THC gets you high by activating the CB1 receptor in your brain. Although THC also has activities at other receptors, getting high 100% depends on the CB1 receptor. It is also responsible for the increase in heart rate caused by THC.

How can we be so sure about this? Because in clinical studies, 3 different CB1 receptor antagonists (, , and ) could reduce both the THC-induced high and the increase in heart rate.

CBD Reduces CB1 Receptor Activation in Cells

CBD is capable of blocking THC activation of the CB1 receptor in cells. For a long time, it was thought to be a . However, this weak affinity for the THC binding site didn’t fully explain the effects of CBD in cells.

Only recently, a showed that CBD actually functions as a by binding to a site on the CB1 receptor distinct from the THC binding site. From this secondary site, CBD is able to change the shape of the receptor in a way that there is less THC binding and less activation of the CB1 receptor. Reduced THC potency was seen at CBD concentrations as low as 100 nM – which can definitely be achieved in humans.

Conflicting Reports of CBD’s Effects in Animals

From the cell data, we would expect that CBD is capable of blocking the effects of THC in animal studies. In reality, the results are all over the place. In some cases, CBD reduces the effects of THC and in other cases it potentiates the effects of THC.

The reason for the conflicting results? There are multiple mechanisms through which CBD can interact with THC. [Read more about the Effect]. Rodents appear to be much more susceptible to a pharmacokinetic interaction where CBD boosts THC blood and brain levels. One is that the timing matters: giving CBD before THC will maximize the pharmacokinetic interaction (potentiating THC) and giving them concurrently will maximize the pharmacodynamic interaction (inhibiting THC).

Clinical Studies of THC and CBD

was the first to combine THC and CBD in a controlled setting. Eight groups of subjects (n=5) were given placebo or 30 mg oral THC combined with placebo, 15 mg, 30 mg, or 60 mg of oral CBD.

This study showed that both 30 and 60 mg of CBD could reduce THC-induced increases in heart rate back to baseline. The psychological rating scale (from 0-4 points) they used showed that CBD brought the effects of THC from a 4 (practically a psychotic state on this scale) down to a 2 (a pleasant high).

The title of the paper says it all: “Cannabidiol interferes with the effects of delta9-tetrahydrocannabinol in man.” This report started the notion that CBD could block the effects of THC. It was highly cited and still continues to be cited today, over 40 years later.

The problem is that this study is wrong. I will show you below that almost all clinical studies done since then have contradicted it.

How can one study manage to stubbornly influence people for decades, even after it is contradicted? Well sadly, this isn’t the only example: One huge impact on the opioid epidemic.

Subsequent Clinical Studies:

1975: A of 20 mg oral THC and 40 mg oral CBD or placebo. No effect of CBD on heart rate or total intensity of high was seen.

1976: A of 25 ug/kg (~1.75 mg) smoked THC and 150 ug/kg (~10.5 mg) smoked CBD or placebo. There was no effect of CBD on heart rate, but the rating of psychological high was reduced from 5.7 to 4.5. When the CBD was smoked 30 min before THC, no effect was seen.

1981: A of 2 mg intravenous THC with placebo or 1500 mg oral CBD given over the previous 8 hours. No effect of CBD was seen on heart rate or self-rated high.

1982: A of 0.5 mg/kg (~35 mg) oral THC wit 1 mg/kg (~70 mg) oral CBD or placebo. No effect of CBD was observed on heart rate, but there was no self-rating of the high. CBD did reduce some responses on a standardized questionnaire of drug effects.

2010: A “naturalistic” where people could bring their own cannabis. No difference in the ratings of being high between people with low-CBD and high-CBD cannabis.

2011: Two studies were published comparing dronabinol (synthetic oral THC) with Sativex (a standardized cannabis extract oral spray with 1:1 THC and CBD). These studies are difficult to interpret since the THC pharmacokinetics were different between the two formulations. However, no obvious effects on heart rate or ratings of feeling high were seen with CBD.

2015: A of 8 mg vaporized THC with 16 mg vaporized CBD or placebo. No effects were seen on ratings of feeling stoned.

2016: A of 5.5% smoked cannabis (~22 mg) with placebo, 200, 400, or 800 mg oral CBD 90 minutes prior. There were no effects of CBD on heart rate or ratings of feeling high.

I have shown the best studies in this figure. To be included, they needed to be double-blind, placebo-controlled randomized crossover studies with self-reported ratings of the THC high. Five studies fit these criteria, although one could not be included since it didn’t report the ratings of feeling high (they only stated that there was no difference with CBD).

Out of these 5 studies, only one (from 1976) showed a significant reduction in the THC high when it was taken with CBD. This study was repeated again, but with smoking the CBD 30 min before THC and there was no difference in feeling high.

Does CBD Block the High of THC?

So does CBD reduce the high from THC by blocking CB1 receptors? The answer is no, CBD will not reduce the high you get from THC. Despite CBD blocking the activation of the CB1 receptor in cell experiments, it does not appear to do this in people.

Although a few studies showed a reduction in psychological effects from CBD, most showed no significant difference in the THC high. This was demonstrated even at very high CBD doses up to 1500 mg (much higher than most people take). I could not identify any trend for the few reports that did see an effect of CBD, looking at THC dose, CBD dose, cannabinoid ratio, or route of administration

The lack of CB1 antagonism was further confirmed by heart rate measurements. CBD did not affect increases in heart rate from THC, an effect also mediated by the CB1 receptor.

Regardless of the cell experiments showing that CBD is a negative allosteric modulator of CB1, we are not seeing much evidence that CBD blocks this receptor in humans. This also means that if you take THC therapeutically, you generally don’t need to worry that adding CBD will block these effects.

Original article appears at www.profofpot.com . Syndictaed by special permission.

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]]> /does-cbd-block-the-high-of-thc-in-cannabis/feed/ 0 Drinking Water to Pass a Drug Test: Does It Work? /drink-water-drug-test/ /drink-water-drug-test/#respond Thu, 13 Jul 2017 14:26:53 +0000 http://www.weednews.co/can-drinking-water-flush-your-system-of-thc-for-drug-test/

Can you flush your system of THC and its metabolites by drinking lots of water or other liquids in order to pass a drug test for marijuana? Or is this myth? Nobody has directly studied it, but we can explore kidney physiology and cannabinoid pharmacology to see whether it is possible. The controversy of drinking […]

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Can you flush your system of THC and its metabolites by drinking lots of water or other liquids in order to pass a drug test for marijuana? Or is this myth? Nobody has directly studied it, but we can explore kidney physiology and cannabinoid pharmacology to see whether it is possible.

The controversy of drinking water to flush out THC

Today I am focusing on another common marijuana drug testing belief: that you can “flush out your system” of THC and its metabolites by drinking lots of water or other liquids (I will refer to this as hyper-hydration)

Don’t confuse this with drinking water immediately before the test to dilute the urine (which is a whole different topic). This is referring to drinking lots of water in the days and weeks leading up to the test with the hope that more THC or metabolites will be cleared out.

The hyper-hydration claim is highly controversial. Ƶ half of websites recommend it and the other half claim that drinking excess water will not help you pass a marijuana drug test.

For example,jezebelԻwikihow fall into the pro-hydration camp (if you are getting your drug testing advice from wikihow, please stab yourself in the eye with a fork):

“Drink 20 to 40 ounces of sports drink per day to restore your electrolytes and keep you hydrated. Drink roughly 1 gallon (3.8 L) of water to flush your body of toxins. Drink the tea and other diuretics throughout the day as well.”

“Drink lots and lots and lots of water—gallons of it—from the time you learn about your test up until the big moment.”

On the other hand, others like Simple Cannabis and “THC Detox Master” (their words, not mine) fall into the anti-hydration camp:

“Drinking plenty of water several days before the test is of no use. Water does not help clean the THC accumulated in the fat cells.”

“…Drinking excess water does not help your body eliminate marijuana and its metabolites from your body, nor does it speed up this process.”

I love scientific controversy! But you probably just want to know whether it is worth the trouble of pissing every 30 minutes for the next two weeks so you don’t lose your job. Fair enough, let’s get this settled.


Basics of drug excretion by the kidneys

[https://www.niddk.nih.gov]

Nobody has ever studied whether hyper-hydration affects elimination of THC or its metabolites. However, we can still use our knowledge of pharmacology and physiology to arrive at an answer for whether drinking a lot of fluids has any chance of helping you pass a drug test for marijuana.

These are your kidneys. One of their jobs is to remove toxins, including drugs, from your blood. It does this by the process of renal excretion. There are several important processes involved in renal excretion that are relevant for our discussion today:

  1. Filtration: Your kidneys use a filtration system where your plasma (the aqueous part of your blood) is filtered into the renal tubule. Ƶ 20% of the plasma that goes to your kidneys is filtered.
  2. Reabsorption: After a molecule is filtered into the renal tubule, it can be reabsorbed back into the blood. Any molecule that can easily cross membranes (and most drugs can) will be highly reabsorbed.
  3. Secretion: Some molecules are are actively pumped  from the blood into the renal tubules by transporters.

How hyper-hydration affects renal excretion

The effect of hyper-hydration on the elimination of THC and its metabolites has not been studied, but we do understand how it affects the processes of the kidney.

Many people would think that drinking a lot of water would increase filtration rate. However,  showed that in the short term, high hydration decreases filtration rate, and showed that drinking extra water has no effect at all on filtration rate over the long term.

Once you understand how the kidneys control the amount of urine production, it actually makes sense that filtration wouldn’t change by drinking more fluids. The water filtered by your kidneys into the renal tubule is almost entirely reabsorbed. Your kidneys do not need to create more urine by increasing filtration, they do it simply by reabsorbing less water.

What is the impact of hyper-hydration on the reabsorption of drugs and other molecules? In several cases, a modest decrease was observed in reabsorption. Why? As water is reabsorbed from the renal tubule to the blood, the drug becomes more concentrated in the urine. This concentration gradient drives reabsorption of the molecule into the blood.

When less water is reabsorbed, there is less of a concentration gradient and also the urine flow is faster, so there is less time for the molecule to cross the membrane into the blood. The net result is that drinking extra water can reduce reabsorption, which may modestly increase renal excretion of some drugs.

There is no evidence that hyper-hydration can affect renal secretion because it is an active process that does not depend on a concentration gradient.

Does hyper-hydration increase the excretion of THC and metabolites?

Here is the basic metabolic pathway for THC (for more details, read the Professor of Pot’s great guide on how THC is metabolized):

THC metabolism

There are two important factors for whether hyper-hydration could possibly increase elimination of THC or any of these metabolites to a significant extent:

Is it reabsorbed? As explained above, hyper-hydration increases renal excretion only for molecules that undergo reabsorption.

Is renal elimination a significant percent of total elimination?: Renal elimination is just one pathway for drug elimination. If other elimination pathways happen much faster than renal elimination, an increase in renal elimination will have little overall effect.

So let’s apply each of these criteria to the four THC molecules:

11-OH-THC and THC-COO-glucuronide do not undergo reabsorption. Therefore, there should not be any effect of hyper-hydration on them.

THC and THC-COOH do undergo reabsorption, so it is at least possible that drinking a lot of water will increase their elimination. However, to what extent? Renal excretion contributes <1% to the total elimination of each. Data from other molecules indicates that hyper-hydration increases renal excretion by about 1/3. Even if we increase renal excretion by 10 times, renal excretion of THC and THC-COOH will still be insignificant relative to other pathways.

Myth busted?

Nobody has yet tested the effect of drinking a lot of water on flushing out THC and metabolites from your body. However, we assessed whether it is even possible using our knowledge of the physiology of the kidney and cannabinoid pharmacology.

Our analysis shows that drinking extra water cannot have a major impact on the elimination of THC or its metabolites. This myth is busted, but you should still stay well hydrated!

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]]> /drink-water-drug-test/feed/ 0 Blunt vs. Joint – Can Science Settle The Debate? /blunt-vs-joint-can-science-settle-the-debate/ /blunt-vs-joint-can-science-settle-the-debate/#respond Mon, 10 Jul 2017 14:26:51 +0000 http://www.weednews.co/blunt-vs-joint-can-science-settle-the-debate/

It is the eternal question for those who like to roll their own – should they make a joint or a blunt? Differences between Blunt and Joint? A joint is when you create a cannabis cigarette with light, semi-translucent rolling paper. A blunt is when you use tobacco paper (same as is used to roll cigars), which […]

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It is the eternal question for those who like to roll their own – should they make a joint or a blunt?

Differences between Blunt and Joint?

A joint is when you create a cannabis cigarette with light, semi-translucent rolling paper.
A blunt is when you use tobacco paper (same as is used to roll cigars), which is thicker and dark brown. This tobacco paper also delivers some nicotine to the user.

Aficionados will swear by one or the other, but you may question whether it really makes much difference. Folk knowledge says that blunts will get you higher, an issue which  and came to the following conclusion:

“Consider this myth busted. Blunts do not make you higher than joints.”

But what science went into their analysis? (Hint: none).

I’m here to tell you that an entire clinical  was performed at Columbia University comparing joints and blunts. They assessed the good effects (how much THC was delivered to the body, how high the subjects felt) as well as the bad effects (increase in heart rate, carbon monoxide levels).

Let’s use science to settle this debate once and for all!

The Scientific Study of Joints and Blunts

Regular cannabis smokers (12 men and 12 women) were recruited to participate in this randomized, double-blind, placebo-controlled study. The study had 6 different sessions. In each session, participants were blindfolded and smoked 3 puffs from either a joint or a blunt containing different THC levels: 0% (placebo), 1.8%, and 3.6%.

The following assessments were made over the next 3 hours after smoking:

Blood samples to measure THC levels
Subjective ratings of the quality of the cannabis
Subjective ratings of the drug effect
Heart rate & blood pressure
Carbon monoxide levels
(Note: For simplicity, I am only reporting results with the 3.6% THC cannabis. However, similar trends were seen across both THC strengths)

Joints vs. Blunts: THC Delivery

No way around it…joints win this category hands down. Smoking joints led to THC levels that were 52% higher than smoking blunts!

Joints vs. Blunts: Getting High

The Marijuana Rating Form was used to assess subject’s ratings of the quality and strength of the cannabis. This form includes items such as “Take Again”, “Liking”, and “Strong”. Not surprisingly (given that joints delivered more THC), subjects rated every item higher for joints than blunts. In fact, the cannabis in joints was rated about 50% better than blunts. This matches up perfectly with the increased amount of THC delivered!

ճrating scale for subjective drug effects showed similar results. This scale measures things like “Good Drug Effect” and “High”.  Subjects rated the positive drug effects to be about 50% better with joints than with blunts.

Another interesting finding was that the difference between joints and blunts was much stronger for women than for men. Not surprising since many other differences have been noted in the effects of cannabis between men and women. For example: 

Joints vs. Blunts: Negative Effects

A mild increase in heart rate is a well known effect of smoking cannabis. In this study, a similar increase in heart rate was seen after smoking either a joint or blunt. This was despite the fact that joints delivered more THC and got subjects higher.

This may be due to carbon monoxide, which also increases heart rate. A higher level of exhaled carbon monoxide was measured in subjects who smoked blunts compared with joints. This is due to the tobacco leaf that are used to roll blunts. Unfortunately, there are many chemicals in tobacco smoke with consequences to your health:

“Carbon monoxide contributes to cardiovascular and pulmonary disease. The elevated carbon monoxide levels observed after blunt smoking may be representative of other toxic gasses and particulates found in tobacco smoke…including carcinogens such as phenols, nitrosamines, aldehydes, and volatile hydrocarbons.”

Conclusion

The results of this study show that joints are the clear winner!

Joints deliver more THC per puff than blunts
Joints get you higher than blunts – with the same amount of cannabis
Joints expose you to less carbon monoxide and other dangerous chemicals
Although I personally prefer a vaporizer, I hope this provides valuable information to those who like to roll

Did you know that smoking is only one of ? And for those interested in the interactions between nicotine and cannabis, I will be writing an article on this soon.

Original article from . Syndicated by special permission.

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]]> /blunt-vs-joint-can-science-settle-the-debate/feed/ 0 Cannabis Tinctures – Four Reasons Why They Work Better Than Edibles /cannabis-tinctures-four-reasons-why-they-work-better-than-edibles/ /cannabis-tinctures-four-reasons-why-they-work-better-than-edibles/#respond Sun, 02 Jul 2017 14:26:57 +0000 http://www.weednews.co/cannabis-tinctures-four-reasons-why-they-work-better-than-edibles/

Two new studies prove that cannabis tinctures have several advantages over traditional edibles. Here is how they stack up. Cannabis edibles come in many forms: tablets, capsules, pretzels, cookies, brownies, gummies, etc. However, cannabis tinctures are fundamentally different—they are a liquid form of cannabis. Tinctures are alcohol based extracts of cannabis that can be drunk by themselves, or […]

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Two new studies prove that cannabis tinctures have several advantages over traditional edibles. Here is how they stack up.

Cannabis edibles come in many forms: tablets, capsules, pretzels, cookies, brownies, gummies, etc. However, cannabis tinctures are fundamentally different—they are a liquid form of cannabis. Tinctures are alcohol based extracts of cannabis that can be drunk by themselves, or added to other drinks or food.

The Problem With Edibles

Dosing of edibles can be challenging. It is difficult to determine when the maximum effect has been reached. Did you dose too low, or has it just not kicked in yet? Absorption of the THC in edibles is different for everybody and is often unpredictable.

Finally, it matters whether you take or after a meal. Taking edibles on an empty stomach changes the ratio of THC to CBD absorbed and can predispose people to experiencing greater anxiety.

However, there is one major disadvantage of taking edibles after a meal. Food will extend the time it takes to start feeling the effects of edibles. It also adds to the variability since what you eat will impact the rate and extent of THC absorption

Tinctures can solve many of the above issues. Read on to find out about new science that proves tinctures are the way to go!

New Scientific Studies Compare THC Tinctures With THC Capsules

Dronabinol is a capsule of synthetic THC that is approved by the FDA as an appetite stimulant in AIDS-related anorexia and to treat chemotherapy-induced nausea and vomiting.

Due to some of the above issues (slow and inconsistent absorption) INSYS Therapeutics has recently developed a tincture of dronabinol that is now . They call it an “oral solution”, but it’s basically the same as a tincture. The main difference is that it is synthetic THC instead of a cannabis extract, which contains a mixture of cannabinoids.

As part of the development of this product, they did several studies comparing the capsule and solution (i.e. tincture) forms of THC. One was under fasted conditions and the was after a high-fat meal.

These studies give us a great opportunity to see how tinctures differ from edibles in controlled clinical trials. Read below to see what we have learned!

Reasons Tinctures Are Better Than Edibles

#1 – Tinctures Provide Better THC Bioavailability

With tinctures, you get more bang for your THC buck. Specifically, 18% more THC was absorbed with a tincture than with a capsule. Not a huge difference, but enough to give it a little extra kick!

The caveat is that this only happens on an empty stomach. A fatty meal will increase THC absorption enough that it won’t matter what form you take THC in.

#2 – Tinctures Have More Rapid THC Absorption

With edibles, THC has to dissolve in your gastric fluid before it is absorbed. Since the THC is already in solution with a tincture, this step is not a limiting factor.

After taking the tincture, THC could be detected in the blood of all of subjects within 15 minutes (empty stomach) or 30 minutes (with food). It took several hours to detect THC in the blood of 100% of patients who took the capsule, whether on an empty or full stomach.

#3 – Tinctures Have More Consistent Absorption From Person to Person

There will always be some variability from person to person in how they absorb THC no matter what form they take it in. However, the ideal edible will have as little variability as possible so that there are predictable effects.

These studies showed that the person-to-person variability in the total amount of THC absorbed was actually similar between tinctures and capsules. However, there were drastic differences in the amount of THC absorbed within the first two hours after dosing. The variability at 30 minutes after dosing, for example, was 3 times higher with capsules than with edibles!

This shows that if two people take the same dose of a tincture, they are more likely to feel the same effects come on at the same time and with the same intensity. With a capsule or other edible, the same two people may feel the effects come on at completely different times or one person may feel it much more intensely.

#4 – Tinctures Have More Consistent Absorption From Time to Time

Imagine you take the same cannabis edible 10 times in a row (well not literally in a row, but on different days). You would hope that the same amount of THC is absorbed each time, but realistically it will always be a little different.

In one study, both the tincture and capsule were given on two separate occasions. This allowed an assessment of how consistently THC was absorbed for each person.

The tincture had a time-to-time variability that was 63% less than the capsule!. This shows that the effects of a tincture are likely to be more consistent each time you take it.

Conclusions on tinctures vs. edibles

One limitation of these studies is that dronabinol capsules and solution contain pure THC – so they could not assess the absorption of CBD or other cannabinoids from tinctures.

Nonetheless, these two studies provide us clear scientific evidence of the advantages of tinctures compared with edibles. Tinctures give us more rapid and consistent THC absorption.

Original article at . 

© 2017 Professor of Pot. All rights reserved. Syndicated by special permission.

 

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]]> /cannabis-tinctures-four-reasons-why-they-work-better-than-edibles/feed/ 0 Alcohol and Cannabis – The Science Behind How They Interact /alcohol-and-cannabis-the-science-behind-how-they-interact/ /alcohol-and-cannabis-the-science-behind-how-they-interact/#respond Fri, 23 Jun 2017 14:26:44 +0000 http://www.weednews.co/alcohol-and-cannabis-the-science-behind-how-they-interact/

Alcohol and cannabis are two of the world’s most popular recreational drugs. It is not surprising then that they are often consumed together. Some people report that they feel pretty good after combining cannabis with a few drinks. There are also many cases of extreme dizziness, nausea, or blacking out. Many people know their limits […]

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Alcohol and cannabis are two of the world’s most popular recreational drugs. It is not surprising then that they are often consumed together.

Some people report that they feel pretty good after combining cannabis with a few drinks. There are also many cases of extreme dizziness, nausea, or blacking out. Many people know their limits for each drug individually, but things are always harder to get right in combination.

There is a saying I heard:

Weed before beer; you’re in the clear.
Beer before grass; you’re on your ass.

Could there be a scientific reason for this?

This combination of drugs has also been a popular topic of scientific study. There are dozens of experiments going back to the 1970’s. I delve into the research to see what science says about this combination.

Effect of Alcohol on THC Levels

Several studies have explored whether alcohol can change the pharmacokinetics (i.e. blood levels) of THC after either smoking or vaporizing cannabis. The results have been mixed, although 2 out of 4 studies showed that alcohol increases blood THC levels. These two studies showed over a 50% increase in blood THC levels after consuming alcohol.

Image: Professor of Pot

One study showed a . In other words, the more alcohol that was consumed, the bigger the increase in THC levels. Since these studies used only low to moderate (about 3 shots worth) alcohol consumption, we don’t know what would happen if even more alcohol was consumed.

These scientists have offered several explanations for why THC levels are higher after alcohol consumption:

  • Vasodilation (the blood vessels are more relaxed) in lung capillaries from alcohol increases THC absorption
  • After drinking, people tend to take deeper hits

Either way, the effect seems to be related to the absorption of THC and thus, if you start drinking after you have already smoked, there should no effect of the alcohol on THC levels.

Effect of Cannabis on Alcohol Levels

Although alcohol appears to increase levels of THC, cannabis has quite the opposite effect on blood alcohol levels. Studies have shown that after consuming cannabis, blood alcohol levels do not rise as fast.

Image: Professor of Pot

One study showed that when smoking a joint 30 minutes after taking a drink, the peak blood alcohol levels were 30% lower. Not only that, but it took twice as long to even reach the maximum blood alcohol level.

This effect could be related to how cannabis slows gastric emptying time (the time for the contents of your stomach to make it to your intestines, where things are better absorbed).

Cross-Tolerance Between Alcohol and Cannabis

The above sections describe what happens with a single dose of alcohol and cannabis. But what happens when you are a regular cannabis user? Science shows that even in the absence of recently consuming cannabis, being a regular cannabis user can affect how you react to alcohol.

Anyone who has been drunk knows that the symptoms include dizziness and lack of motor coordination. But people who drink regularly enough will notice that it takes more and more alcohol to produce these same effects. This is called tolerance.

Image: Professor of Pot

In mice, motor coordination is tested with a device called a rotarod. Basically, they put a mouse on a rod that starts spinning and they see how long the mouse can stay on it before they fall off.

Like a drunk lumberjack, alcohol decreases the performance of mice on the rotarod test. But given regular alcohol, they will develop tolerance and stay on the rod longer.

Here’s where things get interesting: If mice are given daily cannabis, they retain their motor function better after they are given alcohol! When one drug produces tolerance to the effect of another drug, it is called cross-tolerance.

But does this cross-tolerance between alcohol and cannabis happen in humans? Yes!

One that after being given an amount of alcohol which makes infrequent cannabis users dizzy, there was no increase in dizziness for regular cannabis users. Similarly, on a computerized tracking task that measures driving performance, alcohol made infrequent cannabis users score worse, but not regular cannabis users.

Don’t go thinking that because you are a regular cannabis user you can now drive drunk. There was a similar worsening in reaction time for both infrequent and regular cannabis users.

In fact, you may wish to be more cautious of driving after imbibing if you are a regular cannabis user. You may not feel uncoordinated, leading you to think that you are ok to drive, but other key driving skills are still impaired.

Still, how cool is it that being a cannabis user reduces some of the unpleasant effects of alcohol!

Original article from . Syndicated by special permission.

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]]> /alcohol-and-cannabis-the-science-behind-how-they-interact/feed/ 0 Your DNA Can Determine Whether You Pass a Drug Test /your-dna-can-determine-whether-you-pass-a-drug-test/ /your-dna-can-determine-whether-you-pass-a-drug-test/#respond Tue, 30 May 2017 14:29:10 +0000 http://www.weednews.co/your-dna-can-determine-whether-you-pass-a-drug-test/

Image: SNRE Lab on Flickr Countless people spend money on products to pass a urine drug test for cannabis. They don’t know that whether they will pass is already written in their DNA. I recently covered a scientific study on how your genes affect your sensitivity to cannabis. It explained how a variant at a specific place […]

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Image: SNRE Lab on Flickr

Countless people spend money on products to pass a urine drug test for cannabis. They don’t know that whether they will pass is already written in their DNA.

I recently covered a scientific study on . It explained how a variant at a specific place in your DNA can increase how easily you get high.  But it gets even better for these lucky bastards…they are also much less likely to fail a drug test for cannabis!

THC metabolism by CYP2C9

Here is a quick primer in case you didn’t read the  on your genes and cannabis.

Below is the main metabolic pathway of THC. THC is metabolized to the 11-OH-THC. 11-OH-THC is further metabolized to the inactive metabolite THC-COOH, which is the most important metabolite for urine drug tests.

THC,DNA, Metabolism

This metabolism is performed by an enzyme called CYP2C9. The gene for CYP2C9 has more than 50 genetic polymorphisms. The wild-type version (i.e. the most common version) of the gene is called CYP2C9*1. There is a specific polymorphism that has significance for drug metabolism called CYP2C9*3. The CYP2C9*3 variant has significantly decreased enzyme activity.

DNA,THC,Metabolism
Image: Professor of Pot

A  determined that after administering a single oral dose of THC, people with the *3/*3 genotype had 3-fold higher THC levels in their blood than subjects with the *1/*1 genotype.

Effect of CYP2C9*3 on THC-COOH

The CYP2C9*3 polymorphism does not only affect levels of THC in your body. If you look at the above metabolic pathway, you can see that it should also have a strong impact on levels of THC-COOH. In fact, study subjects with the *3/*3 genotype had 3-fold lower THC-COOH levels (below).

DNA,THC,Metabolism
Image: Professor of Pot

Where does all the THC go in people with a CYP2C9*3 genotype if not down the pathway to THC-COOH? There are other metabolic pathways (that I didn’t show) that produce other metabolites. These metabolites mostly do not get excreted into the urine and even if they do, they are not detected by confirmatory drug tests ( for the difference between a screening and confirmatory drug test).

Having a CYP2C9*3 genotype may be even better than you realize if you are a regular cannabis user. Because levels of THC are higher with the CYP2C9*3 genotype (if you are taking edibles) and the high lasts longer (if you are smoking), that means that you can eat lower doses and smoke cannabis less often than people with the regular wild-type CYP2C9 gene and still be just as high.

DNA,THC,metabolism
Image: Professor of Pot

This plot (above) shows the relative levels of THC-COOH if people of different genotypes adjust their doses to get the same amount of combined THC and 11-OH-THC as wild-type users. This analysis shows that if you have the CYP2C9 *3/*3 genotype, your THC-COOH levels will be only 15% of a wild-type person! This is because you only need to take half the dose and your body will only produce one-third as much THC-COOH from that dose.

Urine drug testing for cannabis and CYP2C9 pharmacogenetics

Let’s take a look at how this might play out if you have a drug test coming up. I pulled data from a who start abstaining and have their urine tested on a daily basis. The group I looked at smoked one joint per day on average.

It took 7 days for the urine THC-COOH levels of the average subject to fall below 15 ng/mL, which is the typical cutoff for the GC-MS confirmatory test.

DNA,THC,metabolism
Image: Professor of Pot

I then plotted the expected urine THC-COOH levels of people with the CYP2C9 *3/*3 genotype based on the fact that urine levels should be directly proportional to blood levels (and thus, urine levels should also be 2/3 lower). The results show that it would only take 2 days for the average person with a CYP2C9 *3/*3 genotype to fall below the cutoff, assuming they consume an equal amount of cannabis.

Since we know that people with the CYP2C9 *3/*3 genotype have higher levels of THC, it is likely that they reduce their cannabis consumption to compensate. If these people also reduced their cannabis dose by half, their urine THC-COOH levels would fall below the cutoff in less than a single day after their last dose!

If you have a CYP2C9*3 gene, you are at reduced risk of failing a drug test. You are probably ingesting less cannabis (but still getting just as high) and on top of that, less of the THC is converted to the THC-COOH metabolite that will cause a positive on a urine drug test. You, my friend, have won the genetic lottery!

Syndicated  by special permission. 

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