A CNN program that featured Charlotte's Web cannabis in 2013 brought increased attention to the use of CBD in the treatment of seizure disorders.[64][65] Since then, 16 states have passed laws to allow the use of CBD products (not exceeding a specified concentration of THC) for the treatment of certain medical conditions.[66] This is in addition to the 30 states that have passed comprehensive medical cannabis laws, which allow for the use of cannabis products with no restrictions on THC content.[66] Of these 30 states, eight have legalized the use and sale of cannabis products without requirement for a doctor's recommendation.[66]

Although the 5-HT1A partial agonism exerted by CBD may not be an outright cure for anxiety, it is likely to help many individuals.  Studies conducted on humans with panic disorder note impairments in 5-HT1A receptor function and poor 5-HT1A binding.  The bottom line is that individuals with anxiety could have dysfunctional 5-HT1A activation and may resort to commercialized 5-HT1A partial agonists (e.g. Buspar) as treatments.
Polysomnography recordings were obtained through a computerized system (BrainNet BNT; LYNX Tecnologia Eletrônica, Rio de Janeiro, Brazil). Sleep stages were recorded in periods of 30 s, according to the criteria established by Rechtschaffen and Kales (1968). The following polysomnographic parameters were evaluated: total sleep time (TST, min), sleep onset latency (min), rapid eye movement (REM) onset latency (min), wake after sleep onset (min), wake after sleep onset index (h), apnea index (h), hypopnea index (h), respiratory disturbance index (RDI, h), sleep efficiency (%), stage 1 sleep (%), stage 2 sleep (%), stage 3 sleep (%), REM (%), lowest saturation (%), and baseline saturation (%).
PureKana Natural CBD oil is an unflavored, dietary and nutritional supplement for increased health and vitality. It aims at relaxation and due to its compounds, it seems to have a relatively quick effect. All products go through laboratory testing to ensure safety and potency, and all of their CBD oils are regarded as being non-psychoactive. They also deliver to all 50 states which is a major bonus.

I’ve been struggling with sleep for almost a decade. I started with over-the-counter pills for sleep, then moved to Xanax for sleep. The Xanax works like magic to help me sleep. I’d take three 0.5mg and in 30 mins I’d be in a deeep sleep. However, I would like to wing off pills to sleep for my poor liver and just within the last 2 days have came across this CBD alternative. Given how long I’ve been using a sleep aid and amount I take to sleep, what mg would you recommend taking to sleep? I wanna buy the pen. Also, is there different brands, or strains or whatever like there is with THC “regular weed” or is it all pretty much the same and only separated by MG amount? If there is a different strain of these oils which one is best for pain and for insomnia?


Anti-inflammatory: Many individuals with neuropsychiatric disorders have severe inflammation, particularly neuroinflammation. Neuroinflammation is associated with many causative underpinnings including: air pollution, brain injuries, viruses, and even standard aging.  This increase in inflammation can lead to glial cell and cytokine abnormalities, each of which could contribute to anxiety disorders.  CBD has been shown to reduce neuroinflammation, which in turn may directly improve anxiety, as well as cognitive function and mood.
A geneticist, Kane studies cannabis from a unique perspective—he probes its DNA. He’s an affable, outdoorsy guy with a bright face and eyes that wander and dart inquisitively when he talks. He has studied chocolate and for many years the sunflower, eventually mapping its genome, a sequence of more than three and a half billion nucleotides. Now he’s moved on to marijuana. Though its sequence is much shorter, roughly 800 million nucleotides, he considers it a far more intriguing plant.
When all is said and done, CBD oil is of course relatively new compared to traditional medicine, and therefore a patient with sleep trouble should always discuss CBD with a qualified healthcare professional before using. Also, as we have mentioned it’s important to understand that CBD has not been a clinically-verified form of treatment for insomnia.
For instance, some people report a sense of calm and peace; others report increased anxiety levels and unpleasant sensations. The intensity of these symptoms will largely depend on an individual’s body composition. In addition, marijuana strains feature different levels of oil concentration that also determines the intensity of the outcomes that a user feels after consumption. Some strains are recommended to produce less profound symptoms and reactions.
A 2013 case report conducted in Canada evaluated the beneficial effects of cannabis oil on a 14-year-old female patient diagnosed with acute lymphoblastic leukemia, also known as ALL. For this particular patient, a standard bone marrow transplant, aggressive chemotherapy and radiation therapy were revoked, with treatment being deemed a failure after 34 months. She was extremely ill and severely underweight at this time.
Evidence from animal studies have begun to characterize the details of how CBD acts in the brain, and human studies of patients with and without anxiety disorders are starting to validate CBD’s efficacy as an anti-anxiety treatment. Given the huge social and financial costs of anxiety disorders in the U.S., CBD has the potential to play a significant role in treating a myriad of anxiety-related disorders.
Enter CBD oil: an anti-inflammatory and anti-anxiety compound. I have seen in my own life, and many of my patients' lives, the positive impact CBD oil can have on anxiety. Studies have found that CBD oil is a natural anxiolytic (anxiety calmer) and is effective in treating social anxiety. CBD calms anxiety naturally without the potential side effects of pharmaceutical anti-anxiety medications.
A wide variety of solvents can be used for extraction, such as chloroform, dichloromethane, petroleum ether, naphtha, benzene, butane, methanol, ethanol, isopropanol, and olive oil.[2][9] Currently, resinoids are often obtained by extraction with supercritical carbon dioxide. The alcohols extract undesirable water-soluble substances such as chlorophylls and sugars (which can be removed later by washing with water). Non-polar solvents such as benzene, chloroform and petroleum ether will not extract the water-soluble constituents of marijuana or hashish while still producing hash oil. In general, non-polar cannabis extracts taste much better than polar extracts. Alkali washing further improves the odor and taste.
Dry mouth: As is the case with many other hemp- and marijuana-based products, CBD oil often leads to a condition known as dry mouth (or cottonmouth). This is likely due to cannabinoids altering receptors in the lower jaw that trigger salivation. In most cases, mild discomfort and stronger-than-average thirst are the only issues associated with dry mouth.
Adjunctive option: Many speculate that CBD could bolster anxiolytic effects of various first-line pharmaceutical agents. Since likelihood of CBD interacting with other agents is minimal, it may serve as a novel adjunctive option for those with severe anxiety.  In other words, someone who fails to derive sufficient benefit from a first-line option may find that addition of CBD (on an “as needed” basis) fully attenuates anxious symptoms.
In the end, companies like HempMedsPx are asking consumers simply to trust them. CBD oils are never subjected to systematic testing by any U.S. regulatory body. The FDA regulates all pharmaceutical labs in the country. But cannabis labs like the ones that HempMedsPx and others use are not, because cannabis is not federally recognized as a legal drug.
The main concern about pharmaceutical drugs is that they only treat the symptoms of insomnia – not the root of the problem. That being said, you need to continuously supply your system with certain doses of a drug. This, in turn, may trigger dangerous side effects, such as strong dependence, unpleasant withdrawal symptoms, inflammation, liver failures, and even rebound insomnia.

While these drugs can be effective for many patients, some don’t respond favorably. Certain patients don’t see much improvement, or they can’t tolerate the side effects. Moreover, tranquilizers like Valium and Xanax can be highly addictive. Clearly, alternative treatments are warranted. Could cannabidiol (CBD), the most prominent non-intoxicating constituent in cannabis, provide a viable alternative for currently available anxiety medications? Quite possibly!
“CBD oil has a lifting and relaxing effect on mood with none of the adverse psychoactive effects associated with marijuana,” says Healthspan medical director Dr Sarah Brewer. “It acts via the body’s own endocannabinoid system to promote feelings of wellbeing. It’s a great choice if you’re finding it difficult to relax, as it’s not habit-forming”, she adds, noting that the oil is “particularly helpful for reducing anxiety, promoting relaxation and restful sleep.”
Kane fingers one of his innocuous-looking plants, expressing mild bemusement at the U.S. ban on commercial hemp cultivation. “Hemp produces fibers of unparalleled quality,” he notes. “It’s a tremendously high biomass crop that replenishes the soil and doesn’t require much in terms of inputs. We import tons and tons of hemp each year from China and even Canada, yet as a matter of federal policy, we can’t legally grow it. There are places where farmers in the U.S. can literally look across the Canadian border and see fields that are yielding huge profits.”
CBD interacts mostly with CB1 receptors which are spread throughout the entire body, but they’re found in the highest concentrations in the immune and nervous systems. The interaction between CBD and endocannabinoid receptors, proteins, and other chemicals in the brain, triggers changes in the activity of hormones, and neurotransmitters throughout the brain and the body.
Relevant studies in animal models are summarized in chronological order in Table ​Table1.1. CBD has been studied in a wide range of animal models of general anxiety, including the elevated plus maze (EPM), the Vogel-conflict test (VCT), and the elevated T maze (ETM). See Table ​Table11 for the anxiolytic effect specific to each paradigm. Initial studies of CBD in these models showed conflicting results: high (100 mg/kg) doses were ineffective, while low (10 mg/kg) doses were anxiolytic [59, 60]. When tested over a wide range of doses in further studies, the anxiolytic effects of CBD presented a bell-shaped dose–response curve, with anxiolytic effects observed at moderate but not higher doses [61, 90]. All further studies of acute systemic CBD without prior stress showed anxiolytic effects or no effect [62, 65], the latter study involving intracerebroventricular rather than the intraperitoneal route. No anxiogenic effects of acute systemic CBD dosing in models of general anxiety have yet been reported. As yet, few studies have examined chronic dosing effects of CBD in models of generalized anxiety. Campos et al. [66] showed that in rat, CBD treatment for 21 days attenuated inhibitory avoidance acquisition [83]. Long et al. [69] showed that, in mouse, CBD produced moderate anxiolytic effects in some paradigms, with no effects in others.

Ganja is simply around us more, its unmistakable but increasingly unremarkable smell hanging in the air. Yes, smoking it may lead to temporary laughing sickness, intense shoe-gazing, amnesia about what happened two seconds ago, and a ravenous yearning for Cheez Doodles. Though there’s never been a death reported from an overdose, marijuana—especially today’s stout iterations—is also a powerful and in some circumstances harmful drug.


CBD may help reduces REM behavior disorder in people with Parkinson’s disease. REM behavior disorder is a condition that causes people to act out physically during dreaming and REM sleep. Typically, during REM, the body is largely paralyzed, a state known as REM atonia. This immobilization keeps sleepers from reacting physically to their dreams. In REM behavior disorder, this paralysis doesn’t occur, leaving people free to move—which can lead to disruptive sleep and to injuring themselves or their sleeping partners. Cannabis may also work to reduce pain and improve sleep quality in people with Parkinson’s disease.
Szaflarski explains that cannabis contains about 500 different compounds, some of which—including CBD and THC—interact with certain chemical receptors in the human nervous system. But unlike THC, CBD isn’t psychoactive—meaning it doesn’t cause any kind of a high. Despite that, the US Drug Enforcement Agency classifies CBD (and other cannabis compounds) as schedule I substances, making their sale illegal in many states.

It’s important to remember that Tetrahydrocannabinol oil has psychoactive properties, so it’s still illegal in states where medical and/or recreational use of marijuana is prohibited. Aside from the illegal nature of THC, many health professionals and medical authorities question it’s efficacy as a treatment option since comes with such profound psychoactive effects. In fact, many doctors and researchers see the oil as more dangerous than it is beneficial.
With the re-introduction of CBD in the market, as well as its legalization in the United States and in several other countries across the globe, the production of CBD by various brands and its consumption for numerous conditions is rising. Looking for the best CBD tincture for sleep can be a task pretty time-consuming, and so, you need to hold on to patience. The easiest way to sort out your path towards a suitable CBD oil is by surfing through customer reviews about a particular product.
Typically, pharmaceutical companies making cannabis-based medicines have sought to isolate individual compounds from the plant. But Mechoulam strongly suspects that in some cases those chemicals would work much better in concert with other compounds found in marijuana. He calls this the entourage effect, and it’s just one of the many cannabis mysteries that he says require further study.

As noted, CBD has been found to have a bell-shaped response curve, with higher doses being ineffective. This may reflect activation of TRPV1 receptors at higher dose, as blockade of TRPV1 receptors in the DPAG rendered a previously ineffective high dose of CBD as anxiolytic in the EPM [66]. Given TRPV1 receptors have anxiogenic effects, this may indicate that at higher doses, CBD’s interaction with TRPV1 receptors to some extent impedes anxiolytic actions, although was notably not sufficient to produce anxiogenic effects.
"A CBD company may create a CBD oil, test it, and use the test results to create their label," Bonn-Miller says. "The problem is if they never test their product again, or they test it once a year, you have no idea whether each batch is the same as the first one that they used to create the label. The vast majority of companies are not using manufacturing standards that assure product consistency over time. Companies should be testing every batch they make and tossing batches that don't fall within the specs of their label."
Endocannabinoids (ECS), a group of endogenous cannabinoid receptors that play a key role in memory, mood, brain reward systems, drug addiction, and energy balance. They are also known as »the body’s own cannabinoid system«. Research shows the benefits of the ECS system in fighting depression, anxiety, increasing appetite, and creating feelings of well-being. CBD naturally acts on the ECS system’s signals to increase receptor function and flow. CBD, along with 2-Arachidonoylglycerol(2-AG), is involved in the regulation of appetite, immune system functions and pain management.
Several studies assessed CBD using contextual fear conditioning. Briefly, this paradigm involves pairing a neutral context, the conditioned stimulus (CS), with an aversive unconditioned stimulus (US), a mild foot shock. After repeated pairings, the subject learns that the CS predicts the US, and subsequent CS presentation elicits freezing and other physiological responses. Systemic administration of CBD prior to CS re-exposure reduced conditioned cardiovascular responses [63], an effect reproduced by microinjection of CBD into the BNST, and partially mediated by 5-HT1AR activation [79]. Similarly, CBD in the prelimbic cortex reduced conditioned freezing [70], an effect prevented by 5-HT1AR blockade [87]. By contrast, CBD microinjection in the infralimbic cortex enhanced conditioned freezing [70]. Finally, El Batsh et al. [80] reported that repeated CBD doses over 21 days, that is chronic as opposed to acute treatment, facilitated conditioned freezing. In this study, CBD was administered prior to conditioning rather than prior to re-exposure as in acute studies, thus further directly comparable studies are required.

“CBD coupled with stretching, icing, and foam rolling is a common treatment plan for tendonitis injuries about the knee, such as iliotibial band syndrome,” says Charles Bush-Joseph, M.D., a professor of orthopedics at Rush University Medical Center in Chicago. “Many patients like the fact that CBD is a natural substance. While specific research on the use of CBD in this instance is lacking, many believe that it helps prevent muscle and collagen breakdown.”
Our Editor’s Pick is the tincture from CBDistillery. This tincture is available in five strengths ranging from 250mg to 5,000mg, which accommodates a wide range of THC preferences, as well as 15 and 30 milliliter containers. The tincture has a price-point that is slightly below average, making it a good option for value seekers. The tincture, which is non-flavored, routinely undergoes third-party testing to ensure safety and high quality; the testing results are available on CBDistillery’s product pages.

Selective delta receptor agonists have been shown (in animal studies) to reduce anxiety-like behavior and block anxiogenic effects of stressors.  Specifically, modulation of the DOR in the central amygdala may predict severity of an individual’s anxiety.  There’s reason to believe that allosteric MOR and DOR modulation provided by CBD could reduce anxiety in a subset of individuals – especially when combined with aforestated 5-HT1A and CB1/CB2 effects.
In terms of eye health, cannabis and cannabis essential oil have been linked to a reduction in glaucoma and a prevention of macular degeneration, according to a report published by Dr. John Merritt, Department of Ophthalmology School of Medicine, University of North Carolina. Eye health is one of the major reasons why people turn to cannabis essential oil as they age.
“For those patients who have tried and failed with prescription anti-anxiety medications or want another option for other reasons, CBD is a potential alternative with a good safety profile that offers fewer negative side effects and fewer contraindications with other substances,” Pearson said. “While it won’t work for everyone, it offers a gentler alternative that I have seen work for many people.”
Guzmán leads me around his cramped lab—centrifuges, microscopes, beakers, petri dishes, a postdoc researcher in a white smock extracting tissue from a mouse corpse pinned under bright lights. It’s your typical bioresearch lab, except that everything is devoted to the effects of cannabis on the body and brain. The lab focuses not just on cancer but also on neurodegenerative diseases and on how cannabinoids affect early brain development. On this last topic the Guzmán group’s research is unequivocal: Mice born of mothers regularly given high doses of THC during pregnancy show pronounced problems. They’re uncoordinated, have difficulty with social interactions, and have a low anxiety threshold—they’re often paralyzed with fear at stimuli, such as a cat puppet placed near their cage, that don’t upset other juvenile mice.
Mood enhancement: While CBD isn’t known for provoking a euphoric high, there’s some evidence to suggest that it may enhance mood. Research in animal models notes that CBD yields a combination of anxiolytic and antidepressant effects.  That said, this research cannot be generalize to humans.  If you’re severely depressed, don’t expect CBD to treat your depression.  However, the fact that the drug targets the 5-HT1A receptor and CB1/CB2 receptors suggests that it could improve mood in certain individuals.
Cannabidiol (300 mg), 99.9% purity without THC (kindly supplied by STI-Pharm, Brentwood, United Kingdom) was dissolved in corn oil (Zuardi et al., 1993, 2017; Crippa et al., 2004). The same amount of corn oil was used as placebo. The drug and placebo were packed in identical gelatin capsules. The 300 mg dose was chosen based on previous studies that detected the acute anxiolytic effect of this dose (Zuardi et al., 1993, 2017) and the studies by Chagas et al. (2014b) and Chagas et al. (2014c), in which this dose caused a reduction in the frequency of REM sleep behavioral events and improving quality of life (including sleep) in patients with Parkinson’s disease, respectively. The time of drug delivery was based on previous studies that showed that the peak plasma concentration of an oral dose of CBD normally occurs 1–2 h after ingestion (Agurell et al., 1981; Crippa et al., 2004, 2010; Borgwardt et al., 2008; Fusar-Poli et al., 2009; Zuardi et al., 2017).
Furthermore, there appeared to be increased activation within the left parahippocampal gyrus among those receiving the CBD.  Authors concluded that CBD is capable of eliciting anxiolytic effects that are mediated by limbic and paralimbic brain areas.  It should be noted that similar findings would be reported in a follow-up study published in 2011 – also conducted by Crippa.
These preliminary findings piqued Blessing's interest. For instance, she points to a 2011 study of a few dozen people, some of whom had social anxiety disorder, who were asked to speak in front of a large audience. Researchers compared anxiety levels in people after they took CBD, compared to those who got the placebo or nothing at all. (The participants didn't know if they'd been given the drug or the placebo.)
Anxiety disorders are far more serious and can prevent you from maintaining a normal life. Some have said that anxiety is not a disease or illness, but rather a physiological, psychological-emotional state that occurs when we behave apprehensively. It turns into a disorder when the worry and the anxiety it creates interfere with your lifestyle. Ongoing anxiety can lead to numerous medical illnesses and even mental issues, if not dealt with.
One study comparing the effects of THC and CBD even found that, while THC increased anxiety by activating the neurotransmitters involved in the "fight or flight" response, CBD actually repressed autonomic arousal—or the nervous system response associated with sudden increases in heart rate or respiration. In other words, CBD is ideal for people looking to relax and unwind—not get out of their minds.
Bergamaschi, M. M., Queiroz, R. H. C., Chagas, M. H. N., de Oliveira, D. C. G., De Martinis, B. S., Kapczinski, F., . . . Crippa, J. A. S. (2011, February 9). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology, 36(6), 1219-1226. Retrieved from http://www.nature.com/npp/journal/v36/n6/full/npp20116a.html?foxtrotcallback=true
Cannabidiol (CBD) is a chemical compound found in the cannabis and hemp plants. CBD is one of over 100+ cannabinoids that are responsible for the therapeutic properties found in cannabis and hemp. CBD is widely known for its healing components and is used to treat a variety of conditions. It is generally accepted that CBD works best in conjunction with other cannabinoids and terpenes found in these plants. This potent combination — the entourage effect — is what makes the healing properties so exciting.
Harper was diagnosed as an infant with CDKL5, a rare genetic condition doctors only discovered in 2004 and that afflicts roughly 600 people worldwide. The disorder shares its name with the minute particle of DNA it affects, a gene responsible for the production of a protein crucial for neurological development. Symptoms of CDKL5 include intellectual disability, developmental delays, breathing and vision problems, limited or absent speech, poor muscle tone, and, perhaps worst of all, frequent seizures.

For example, the six hemp oil companies the FDA had investigated in February had explicitly advertised CBD products for use in the “cure, mitigation, treatment, or prevention of diseases.” The agency sent warning letters to the companies, ordering them to change their product labeling or face potential legal action. Then, in May, the FDA announced it was excluding products containing cannabidiol from its definition of dietary supplements altogether. Hard, the spokesman for Medical Marijuana, Inc., said the company views “these developments as positive because this allows the debate regarding CBD to come to the forefront.” He characterized the FDA’s May announcement as “an opinion” and added, “Medical Marijuana, Inc. and HempMeds, along with industry associations, are working on determining how we can come to a mutual understanding on the matter with the FDA.”


Let's start with the most officially proven medical use of CBD. Earlier this year, the FDA approved the first-ever drug containing CBD, Epidiolex, to treat two rare forms of pediatric epilepsy. To get to that point, the drug's manufacturers had to do a whole lot of randomized, placebo-controlled trials on humans. They had to study how much children could take, what would happen in case of overdose, and any possible side effects that would occur.
Some users speculate about appropriate dosages or methods of application—including whether or not a small amount of THC boosts CBD’s effects, or whether different methods of administration lead to quicker or more significant effects. Some CBD producers also claim that it has a cumulative effect, and so needs to be used regularly to produce a benefit. But Grant says it’s tough to say at this point exactly how people should (or shouldn’t) be using CBD.

Hi. I really do believe it depends on the mg & ratio of the CBD to THC. My first try at high CBD : low THC tincture oil was with Humboldt Anthropology 16:1. I started off with 2 drops twice a day after 3 days I went to 4 drops twice a day. After a few daysof that I went up to 6 drops and then 8 drops and then 10 drops twice a day. 10 drops twice a day was a perfect dosage for me. FINALLY no pondering worries or fears from all the “what if’s”. If I didn’t want to think about something I had control over not thinking about it. It was an amazing feeling. It was complete FREEDOM. Sadly the dispensary I use no longer has the Humboldt Anthropology 16:1 tincture. Last week I moved on to my first trial with a different brand. They recommend Jayden Juice 28:1 tincture 2 to 3 drops twice a day. Very 1st dose tried 4 drops(because I was up to 10 with my other tincture) and felt weird. Kinda spaced or like a head change. Not sure if it was my tincture or the fear (my anxiety) of trying something different. Didn’t like that feeling one bit. My second dose for the day I took 2 drops. With that said I took 2 drops twice a day for a couple of days. I could feel the anxiety stirring around within me. That warm tingling feeling in my chest and arms. All the “what if” thoughts are far off in the back ground of my mind. Crazy thing because I haven’t felt that feeling in over a year while taking Humboldt Anthropology 16:1 even after the passing of our son this past Aug. As of yesterday I started 3 drops twice a day with the Jayden Juice 28:1 that I currently have. Praying that I can make this work for me. $80 for .05 oz is a tad pricey, “what if” it doesn’t work for me.
I had absolutely no problem chatting with the grocery store clerk at the cash register and actually found myself enjoying the chat (not something that usually occurs).  Thereafter, I drove home and cooked myself dinner.  My friend sent me a text to hang out at like 10:00 PM and I was feeling a bit anxious, so I decided to pop 2 more CBD capsules at around 9:30 PM.
Every person has their own tolerance and reactivity threshold. Hence, we would advise you to consult your doctor who can set the CBD dose you need to put you into sleep. However, the best way to calculate your customized dosage is by starting at a low amount and increasing it gradually thereon, until the desired effects are met. Be careful not to overdose.
@lalyfa In 2010 I went off a cocktail of psychotropics including antidepressants, antianxiety and antipsychotics cold turkey. The meds were wrong for me and the withdrawal was severe and I rarely slept, had RLS, neuropathy and cranky beyond words. Some of these meds took 9+ months to clear my system. Be sure to follow doctor's advice. I did not have a doctor at the time and would not go to the ER knowing it would have resulted in more abuse. Not an intelligent thing to do and not sorry I made the choice even though the experience was horrific and would not reccomend anyone go this route. As to how long the withdrawal lasts the best thing is to discuss this with a pharmacist as this is where their training is and they understand much better and be of help. Wishing you the best.
Several complexities of the eCB system may impact upon the potential of CBD and other CB1R-activating agents to serve as anxiolytic drugs. First, CB1R agonists, including THC and AEA, have a biphasic effect: low doses are anxiolytic, but higher doses are ineffective or anxiogenic, in both preclinical models in and humans (reviewed in [33, 45]). This biphasic profile may stem from the capacity of CB1R agonists to also activate TRPV1 receptors when administered at a high, but not low dose, as demonstrated for AEA [46]. Activation of TRPV1 receptors is predominantly anxiogenic, and thus a critical balance of eCB levels, determining CB1 versus TRPV1 activation, is proposed to govern emotional behavior [27, 47]. CBD acts as a TRPV1 agonist at high concentrations, potentially by interfering with AEA inactivation [48]. In addition to dose-dependent activation of TRPV1 channels, the anxiogenic versus anxiolytic balance of CB1R agonists also depends on dynamic factors, including environmental stressors [33, 49].
Human activities—including pollution, deforestation, overpopulation, poaching, warming oceans and extreme weather events tied to climate change—are predicted to drive so many mammals to extinction in the next five decades that nature will need somewhere between 3 to 7 million years to restore biodiversity levels to where it was before modern humans evolved, according to an alarming new analysis published Monday in the Proceedings of the National Academy of Sciences.

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