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Cannabidiol in Anxiety and Sleep: A Large Case Series (nih.gov)
196 points by mettamage on July 3, 2019 | hide | past | favorite | 149 comments



I have some current experience with my adult daughter suffering with severe anxiety. I started looking for over the counter treatments and found studies that used magnesium glycinate successfully as a treatment and it has worked wonders for her.

She takes a 300 mg tab and in 20 minutes she's completely calmed down. It only lasts for about four hours but the effect is amazing.

The downside is it can cause diarrhea when taken every four hours but if she eats a couple bananas a day (for the fiber) that's not an issue.

She's also been experiencing auditory hallucinations (hearing voices) and I found a study that showed CBD helping with that, so I got her to start taking that too, and it's worked amazingly well for her to deal with that. If it also helps with anxiety that's all the better for her.

Her birth mother was diagnosed as schizophrenic about a year after my daughter was born so my daughter is probably dealing with that too, but the drug the doctors gave her mother 35 years ago (haloperidol) didn't work near as well as the magnesium/CBD my daughter is taking and the side effects were vicious. That shit turned her mother into a slobbering zombie.

I took my daughter to a mental health facility yesterday to get evaluated and we told them she was taking the magnesium glycinate for anxiety and CBD for "the voices" and they didn't tell her to stop or prescribe any pharmaceutical drugs for her. They just told her to start "Mindful therapy" sessions with a doctor there.

I've been smoking herb for about 46 years pretty much daily and have never felt anxious, but I've known a few people who have. I've attributed that to all the reefer madness that's been shoved at us for so long, but it could be it affects some people differently than I and all my herb smoking friends.

I don't feel any effects at all from taking CBD, but I don't have any of the symptoms it's used to treat effectively and it could be I have plenty enough in my system from the weed I smoke anyway.


I get anxiety when I smoke and am way too young to attribute it to any sort of “reeder madness” - so it’s definitely a thing. I don’t smoke super often, and don’t always get anxiety when I do, but it definitely gave me terrible anxiety when I was younger.

If anyone else gets anxiety when they smoke, I recommend smoking sativa instead of indica (nicknamed “in da couch” because of its anxiety effects). I was given the tip from a stoner friend, and it’s fsirly true in my experience.


The same happens to me, but the next day I feel a significant decrease in anxiety. I wonder if the pro-anxiety effects of THC are overcome by the anti-anxiety effects of CBD over time (e.g. the anxiety effects of THC last for a few hours, the milder anti-anxiety effects of CBD last for a couple of days).

FWIW, I have the opposite reaction to different strains. Sativa gives me anxiety, while indica makes me want to relax and take a nap. Really hope researchers can start testing effects so we can figure out where this can help anxiety. So many people I know struggle with it; I'd love for them to have a way to treat it.


I hear this repeated a lot in different variations, some people say the exact opposite, but it's untrue.

There's no real definition of what a '100% sativa' or '100% indica' even is. All we have to go by are characteristic leaf patterns between indica/sativa. In short, the whole 'indica body buzz' thing is unfounded. In fact, I remember hearing the EXACT opposite of what you heard a few years ago. I was told that sativa caused anxiety and indica was more calming.

The reality is that the only differences between strains are in combinations of THC to CBD. Plants with higher CBD and lower THC will be more 'calming' and plants with higher THC and lower CBD will get you more high, which can produce more anxiety in people sensitive to THC.


This is a good first-order approximation, but there are other cannabinoids which influence the effects: CBN, THCV, and others [0]. Additionally, based on first-hand anecdata, I think there is good reason to believe that the terpene profile can have a big effect on the experience, as well as the flavor [1].

But, yeah, if THC causes anxiety for you, try to never go above a 1:1 THC:CBD ratio. For comparison, most sativas are around 200:1 (20% THC : .1% CBD). Since CBD is legal over the counter, you can usually enforce this ratio, regardless of the THC source.

[0] https://www.leafly.com/news/cannabis-101/list-major-cannabin... [1] https://www.leafly.com/news/cannabis-101/terpenes-the-flavor...


I agree I was oversimplifying, of course there are other cannabinoids in weed that can affect the high. What doesn't though, is how sativa or indica a strain is.


In general the rule of thumb is sativa is a head high and indica is a body high.


woosh


1) you got the 2 mixed up, it's indica that's the in-da-couch. Sativa is the brain-high.

2) there's little evidence to prove that sativa/indica strains affect your high. The curing, drying, growing of each individual plant alters the THC-CBD-CBG ratios way more than strain or species.


Point number 2 is utterly untrue as any experienced cannabis enthusiast could tell you. Even if people don't know the strain or what the effects are it's pretty reliable that it will either energize them or send them to sleep.


It's not untrue, there is no definition genetically of what a pure sativa/indica strain even is, see my other comment here.


What they were saying is anyone with experience in cannabis can tell you after a few minute of smoking if it's sativa or indica. Doesn't matter if there is no genetic definition, there are obvious differences.


There aren't, and those subjective reports can't tell us anything related to how 'sativa' or 'indica' some strain is. The only thing that affects high is CBD-THC ratios (and possibly other alkaloids) & those are independent of strain.


Interesting - I had assumed the opposite! I picked up a few different blends a while back hoping to address some (relatively mild) social anxiety and it worked well at first but later started giving me horrible anxiety (oddly only later that night - I'd take a small dose in the morning and be fine all day, then freak out from 1am to 4am.) Tried a bunch of different blends of thc:cbd with little luck, but I was sticking mostly to indica thinking sativa was more likely to cause anxiety.


I think they have this the wrong way round. Indica is known for its relaxation effects. Couch lock isn't due to anxiety but relaxed passivity, and sativa strains tend to promote overthinking and paranoia in those (inc. myself) prone to it.


No. It depends on the person entirely and if you start digging you will find about equal distribution of people who are calmed by a sativa and people who are calmed by an indica. I personally suspect that people who feel calm from a sativa are a little ADHD and it seems to make them think better and more calmly and indicas make them much more anxious because it exacerbates and existing condition.


anecdotal, but i am certainly an individual with adhd and i personally find strains marketed as indica dominant to be far more effective for anxiety relief and just general functionality. it also may just be a random correlation, but i always recalled seeing higher levels of cbd in indica based strains when I lived in Washington and the actual levels of cbd and thc in the product was listed on the packaging. i certainly don't think this is strong evidence that such a thing is the case, in an overarching empirical sense, but i can at least say, with confidence, that for me, indica dominant is much less anxiety inducing


This kind of matches my experience - the anxiety I get is from feeling like my mind is slowing down / not totally working properly and not knowing if it will ever come back. I think I am a bit ADHD, and caffeine has a kind of calming effect on me as well, so might be worth trying a sativa blend.


I'm am glad you are helping your daughter thought this . This disease is such a cruel thing to have .

I would like to offer some extra info .

Since you are looking for OTC . Both NAC and SACROSINE have a lot of great research when it comes to schezophrenia. It seems to work for some but not others.also new research into TMG (betaine glycine) is also interesting

There is also a new drug on the horizon that doesn't work on the dopamine receptors and has much less side effects than what's currently

SEP-363856 helps treat negative symptoms of schizophrenia such as Inability to experience pleasure, Lack of interest in relationships, Lack of motivation. 5HT1A and taar1 agonist

https://www.medscape.com/viewarticle/913348

MIN-101 - a ~20% BDNF increase. Treats negative symptoms of schizophrenia. 5HT2A and sigma2 receptor antagonist.

Min-101 has a targeted release of 2021/2022. After they have completed their 12 week phase 3 trial, they will do a 36 week phase 4 trial. SEP, should also be available sometime in those two years as well.

Hope your daughter finds peace


I have a mutation which results in impaired BDNF and I do suffer from anxiety; so far buspirone seems to work, but I was considering SEMAX/SELANK for the BDNF increase, do you know anything about that?


I can tell you it'll make your hair fall out.

And maybe make you 20% less anxious/more focused, but honestly it's hard to say... actually, in retrospect I never experienced acute anxiety when I was experimenting with it. Certainly worth a shot.


Does the hair come back after you stop using it?

I already have moderate male pattern baldness :)

20% seems ok to me, buspirone is not that great either, but I never experienced panic attacks while on it(actually I only experienced panic attacks while on stimulants), and if I had another option like SELANK/SEMAX with the BDNF boosting bonus, that would be great.

I'll give them a shot.


I'm not sure but I think it's permanent. If you don't mind getting balder than you currently are, great.


Semax can make your hair fall out slightly selank doesn't . Ive heard good stories about both . Try them both out but start with semax . Do it long term .

Fasting can increase bdnf by 3.5 times . Research intermittent fasting and also long term fasting (48 hours) .

There is just so much that can increase bdnf but as a rule of thumb when it comes to herbs . Studies mostly are short term and just not as good .

I recommend coming over to the nootropics subreddit and research/ask there


I tend to worry a lot and it's fine during the day, but it really amps up at bedtime and I lie awake with racing thoughts. It sounds worth trying the magnesium glycinate (at least for a week) - from what you say taking it around half an hour before bed will let me know if it helps or not?

For the record I've tried melatonin etc - the issue is NOT being tired or even sleepy. My brain just refuses to shut off, to the point where I've started seeing things while awake, when one part starts dreaming and the other refuses to. This usually results in me jumping awake with an extra load of adrenaline to delay my sleep.


IANAD. The glycerinate does have a better absorption rate but and taking over 300mg a day regularly apparently has the potential for side effects (beside those bowel effects) - at least that's what I've gathered looking into Mg supplements previously.


Yes, it's a trade off and she needs to adjust the doses down if she can.

Right now she's in shit shape mentally after being ditched by her fiancé so hopefully time will help her get over that, but truly amazing how well and quickly the magnesium glycinate helps calm her down.

Physically she's as strong as can be. She's a level II Crossfit trainer and stronger than me. We're going try transitioning towards getting the magnesium from food sources if we can get her over this hump. She eats healthy, but she's obviously not getting enough magnesium and burning it up quickly right now.


You can use Mag Oil as another way to get Mg into the body. Its basically Magnesium Sulphate aka Epsom Salts mixed with water and rubbed on the skin. If its really concentrated it will sting the skin, but dilute to reduce the stinging effect. Alternatively soak in a bath with Magnesium Sulphate. https://www.epsomsaltcouncil.org/wp-content/uploads/2015/10/...

Any sulphate can be absorbed through the skin, so soaking in copper sulphate will get more copper into the body which is useful for all types of Collagen. Copper will also make smokers feel like they are smoking their very first cigarette, ie they will feel nauseous if they smoke within 30mins of taking a copper supplement. I wouldnt advise applying copper sulphate directly onto the skin though as it will debride the skin and is now only used by the US Military for cleaning extreme wounds.

Magnesium irritates the lower bowel hence the diarrhea, so if taken orally, its better to take little and often through the day rather than one big supplement for a day, and always take after eating because tablets breakdown in the gut and get into the blood stream quickly.

Magnesium is also used to make ATP (Adenosine triphosphate) which helps provide cellular energy so being superfit, her demands for Mg will be higher than a sedate person. Taking Potassium also helps the cells take up glucose, amino acids and other nutrients including magnesium whilst sodium makes the cells take up just water, so in a way sodium starves cells at a cellular level, which could help contribute to a variety of problems including anxiety. To get your daily potassium intake of 4.7grams, you would need to eat 11 large banana's a day. One sign you are deficient in Potassium is you crave sugary foods after eating, but if you supplement around >2g with potassium (chloride/bicarbonate) your sugar cravings will go.


Has she checked her magnesium blood levels?

It might be that she's not actually deficient, but magnesium is a NMDA antagonist (afik) and the axiety relief might come from that.

I'm just saying that magnesium might be a temporary fix, but she might get magnesium "poisoned" (if that's a thing) and you should search for an actual drug that has the same mechanism of action as magnesium does, but something that doesn't build up in your system.


Very interesting, I have noticed a major (albeit fun) experience of mania from CBD, followed by extreme rebound anxiety after cessation following a period of taking it for a while.

THC-heavy strains on the other hand, seem to have no bad effects.


Just a heads up. The glycine(of the glycinate) might be helping just as much as the magnesium. Glycine is relaxing and theorized to help with schizophrenia. (through nmda signalling)

If you're interest in other supplements that have preliminary evidence for helping with schizophrenia are bacopa and sodium benzoate are maybe worth a try.[0][1]

- Obviously talk to your doctor about it. https://www.ncbi.nlm.nih.gov/pubmed/29397899 https://www.ncbi.nlm.nih.gov/pubmed/?term=bacopa+schizophren...


> sodium benzoate

Note that in combination with vitamin C, sodium benzoate may form benzene, which is toxic. But perhaps this is only relevant if you store them together, and at higher temperatures (?)

https://en.wikipedia.org/wiki/Sodium_benzoate#Association_wi...


+1 for Mg. I prefer the citrate salt as I find it faster acting and doesn't give me the same digestive issues, but it's so damned effective for general anxiety I even keep a bottle in my desk at work!


What brand and kind of CBD do you use ?


It's high CBD content oil that's got a private label brand. I'm not familiar with the supplier, but the supplement store we buy it from is locally owned and very reputable. My daughter works for them on occasion. They also sell CBD buds and she says she likes those better than the oil.


So it's under the tongue intake ? or is it vaporized and inhaled ?

Does she feel other improvements as well ? eating, sleeping or else ?


People take cannabis to help them manage the effects of schizophrenia but corrupt media used to play it other way around. Cannabis causes schizophrenia! If there was justice in this world, then all the editors allowing this should rot in jail.


Dude. CBD is antipsychotic[1] and thus might help people with schizophrenia. THC is psychoactive [2] and should probably be avoided by people with schizophrenia.

[1] https://www.ncbi.nlm.nih.gov/pubmed/22716160 [2] https://www.ncbi.nlm.nih.gov/pubmed/28492950


I think that's what the poster is saying. I believe "Cannabis causes schizophrenia!" should be in quotes.


Yes, but the replier is saying that THC, the primary active compound in Cannabis, can in fact worsen some of the symptoms of schizophrenia. As someone with Type I Bipolar, which has many similarities to schizophrenia, I agree that this is often the case.


That's why it should be legal so people who need it won't have to fiddle with the dealers. Obviously big pharma pays a lot so that won't happen.


I'm 100% with you there.


This is exactly what I meant. Thanks for sharing your experience.


The dosages of CBD used in this study are far, far, too low to have any effect. Just like most CBD dosing in commercial situations. Usually scientific investigation use the actual useful dosages of 300-600 mg in humans. I guess these guys didn't do the required background review beforehand.

CBD is not active at the CB1 or CB2 receptors. It has very low affinity for them. It has moderate affinity for the serotonin-1a autoreceptor (that the anti-anxiety medication buspirone also targets). But only at very high dosages (ie, 300mg+).

So... this study has only really tested the placebo effect.

edit: I finished reading the journal article and it turns out they didn't use clinically relevant doses because it'd cost too much. So they decided to just go the placebo route.

>The doses used in this study (25 mg/d to 175 mg/d) were much lower than those reported in some of the clinical literature (300 mg/d to 600 mg/d)12–14,17 for 2 reasons. The first is that in our experience lower doses appear to elicit an adequate clinical response. Second, the current retail cost of CBD would make the use of 600 mg/d cost prohibitive.


Yeah, the cheapest CBD I could find on Google was ~$30/g (pre- tax, shipping, etc). Good luck convincing people to spend $600/mo on their sleep!

(I can already hear the HNers coming out of the woodwork to attest to their willingness to do so, how sleep is 1/3rd of your life and so if you're spending < 1/3rd of your income on it you're actually getting a great deal, and how it would actually save them tons of money to sleep a bit better and with a little less anxiety...yada yada..

but the vast majority of people can't do that)


Ha, your parenthetical definitely anticipated me.

If I could RELIABLY score a solid 8 hours every single night, I would call $600/mo steep — but worth it.


Also says something about the general cross section of HN users that $600/mo is "steep but worth it". There a lot of people for whom $600/mo is wildly unaffordable for anything, even essential medical care.

(FWIW, I'm with you, if I could wake up well rested every morning, I'd drop $1K/mo or more without a second thought)


When you're taking 600mg of CBD it's likely there's at least a handful of mg of THC 'contamination'; enough to be an active dose. Part of the reason it's expensive is separating the two effectively.


I bet you people would use it if it was their last resort to getting a good rest.


No doubt. Insomnia is merciless. It's just that, for a lot of people, this approach will be out of their reach. Not that that means we shouldn't try to make it affordable, of course.


Is there a more trustworthy study we should look at?


This is a case series and literally has no control group. What's the background rate of people getting better without using CBD?


No control group, no placebo, not blinded, not double-blinded, small sample size.

The only possible real takeaway from a study like this is that it appears to support undertaking a larger, more expensive & more robust study on in determining whether CBD may have benefits in treating anxiety and insomnia.

Seeing a candidate treatment at such an incredibly embryonic stage being voted to the top spot of hacker news, to me, suggests our HN audience has significant room for improvement in ascertaining the quality or implications of published scientific studies.

EDIT: In particular, a risk here is that readers here might feel encouraged to try smoking cannabis for self-treatment of anxiety or insomnia, which is quite a different thing than taking CBD itself. Specifically, recreational cannabis is intentionally grown to have a high THC content, and THC can and does have negative consequences for those people suffering from anxiety.


> a candidate treatment at such an incredibly embryonic stage being voted to the top spot of hacker news, to me, suggests our HN audience has significant room for improvement

It's a super hot topic right now because these shops have suddenly popped up all over the country - including in cannabis prohibition states - and some of them must be making a good amount of money for there to be so many. Business minded people are acutely interested in where this thing is going long term, so any data at all is seized upon, no matter how dubious.

This, of course, makes comments like yours even more important and appreciated.


Not only that, the CBD was given in addition to normal treatment: "A large retrospective case series at a psychiatric clinic involving clinical application of CBD for anxiety and sleep complaints as an adjunct to usual treatment."

This study design prevents us from making any strong conclusions on CBD. Was it the normal treatment that helped, or the CBD? With no controls, and no separation of standard treatment and the new intervention, we can't conclude anything. In defense of the study authors, they don't make a strong conclusion, and call for controlled clinical trials. But I doubt people talking about the study will be that restrained.


Importantly:

Inducing unconsciousness isn’t the same as sleep. Many chemicals that knock you on your ass also disrupt sleep architecture. A study that doesn’t at least throw a polysomnography on the patients to make a gesture in the direction of “they’re getting actual sleep” isn’t worth the paper it’s printed on.


A large case series[1] on reviewing dubious publications on Cannabidiol indicates substantial increase in anxiety among critical thinkers. A causative correlation[2] is concluded by the series.

[1] https://news.ycombinator.com/item?id=20340937

[2] https://www.xceleratemaths.com/algebra/images/graph-y=x.gif


I was kind of surprised to read that CBD wasn’t studied that much in the firzt place.


That's what happens when a drug is Schedule I without medical or scientific basis (it was merely racism).


There will be proper controlled trials soon, there is no substitute.

However, it's worth noting that most complementary therapies actually do nothing - homeopathy is the classic example. Of course, we know many people find them helpful for a variety of reasons, but they actually do not have any physiological or pharmacological effect. CBD on the other hand is definitely a psychoactive substance, which may have side-effects. I think this actually makes it more likely a priori that it is a useful treatment. Put it this way, say we didn't know about CBD at all, if a drug company discovered CBD in some kind of drug screen, they would definitely test it and advance it into clinical trials.


Stupid question but I’ve always wondered this - I hear Cannabis is used for anxiety relief but doesn’t smoking marijuana induce anxiety? Everyone I know who has smoked weed agrees with my experience - they’ve encountered some level of anxiety and paranoia. So, how exactly does weed help in reducing anxiety?

Edit: Follow up question -> Is weed used to treat anxiety during the high or when you are normal (and have general anxiety when not smoking pot)?


As others have mentioned, it's the THC component that can cause anxiety. I have high anxiety and THC usually makes it worse, but that's just temporary. I find that THC is bringing subconscious worries and pains to the surface, and if I actively process them, then I come out of the high feeling extreme relaxation and peace, more than I ever got from pure CBD.


Just a data point. I dealt with anxiety my entire life, and too much weed absolutely destroys me but small amount of weed definitely calms me down. When I smoke too much weed, it really doesn't feel like my anxieties deep down are surfaces. It feels like my brain is making up new stupid things. To me, weed is a very strong sensory experience. When I'm too high it almost feels I'm hearing too much, feeling too much, seeing too much and that disorients me. Also due to my anxiety I've dealt with dp/dr in the past (luckily I don't have this problem any more) and too much weed induces this dp/dr back.

When I was young and stupid I did get too high and got bitten by it. One needs to learn lessons the hard way. You need to be respectful to drugs, try understand the science behind how substances affect your brain and start small and increase doses infinitesimally as you feel comfortable and as you decide it does not affect your life negatively in any way objectively.


You probably need to try a strain with less THC and more CBD (like a 2:8 ratio).


Yes nowadays I smoke mixed CBD-only and THC-only strains this way I can make custom ratios. Weed's been orders of magnitude more comfortable since I started doing this.


Another data point: I have anxiety and weed/hash reduce my anxiety, it helps a lot with falling asleep while I'm awake but I'm known to scream while sleeping under the influence; another time I was sound asleep near a friend who was snoring and his snoring woke me up and I was convinced he was in fact drowning in his own vomit and I slapped and shook him and tried to get him on his side, after I realized he was fine, I happily went back to sleep as if nothing happened.

I also had visual hallucinations, visual/auditory synesthesia once from a high dosage of hash, so I might be an outlier.


What kind of made up anxiety have you encountered? I ask just to understand. I've never run into an anxiety after smoking weed that wasn't rooted in reality. I find it helpful for the same reasons the previous poster stated.


Like one time I accidentally dosed my weed wrong. I prepared a bowl with super-high THC strain (I live in a legal state) when I was trying to smoke a 1:1 THC:CBD strain (I wasn't trying to get high, I was trying to medicate against my chronic inflammation problem). I vaped the entire bowl. Continued to watch Portlandia and 30 seconds in, I realized something is wrong and I can barely keep my eyes open. After managing the initial disorientation, I got up to take a shower because my heart was beating at 150 bpm so I wanted to distract myself. When I got up I heard someone talking outside. It sounded like it's my coworker's sound. I got worried for some reason. I was worried that my coworker would see me high and think I'm a "loser stoner" getting high alone. Of course it was just my neighbor talking on his phone outside. Anyway, I never felt like this before or ever since. This was a unique paranoid experience I felt at that moment.


That the airplanes constantly flying over your home, which you can hear but not see, are actually missiles being lobbed across the world as countries that are not your own duke it out.

Not completely rooted in reality, and you’ll probably calm down as you come down. But now you feel a brief stab of anxiety any time you hear an airplane fly overhead.


For me it's just the feeling of anxiety, no specific anxiety inducing subject is running through my head and no paranoia. When I eat edibles (which I do rarely and almost always regret it) the anxiety is worse, I get really cold and my whole body shakes.

I stick to small amounts of vaped weed and I can enjoy it


This is a good way of putting it.

I view THC as having an 'echoing' effect of whatever I am feeling. If something makes me laugh, the feeling of laughing will cause more laughter. If I am feeling anxiety, the feeling of anxiety will cause more anxiety.


That's absolutely true, weed is a big enhancer.


I feel like it makes your inner Voice louder.

some days you can control your inner voice better than others

Also thc tolerance helps, once you get the tolerance up it is a lot less anxiety inducing and more relaxing.


In my experience, if I smoke a very small amount of weed (like literally one hit) it can relax me and make me less anxious. It slows things down, and can just generally numb some of my underlying anxieties.

However, it doesn't take much for me to cross that threshold where it can make me extremely paranoid. Usually this is what I call the "will I be stuck this way forever" threshold, where I get stoned to the point where I start to freak out that I will never be able to think clearly again.

So my point is that, at least for me, it is dose dependent, and I could easily imagine a scenario where CBD can act to relax your nervous system responses but not alter your thinking to the point of it becoming a foreign and potentially scary experience.


This comment made me curious and I did some googling for studies on the anxiogenic (anxiety-increasing) effects of THC. Some interesting resuts:

THC's anxiety inducing effects are (at least in part) caused by CB! receptor activity in the right amygdala. "Fourteen healthy males were studied with fMRI twice, one month apart, following an oral dose of either delta-9-THC (10 mg) or placebo, while they performed a fear-processing task. Baseline availability of the CB1 receptor was studied using PET with [11C]MePPEP, a CB1 inverse agonist radioligand. Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. Both these effects were positively correlated with CB1 receptor availability in the right amygdala. These results suggest that the acute effects of cannabis on anxiety in males are mediated by the modulation of amygdalar function by delta-9-THC and the extent of these effects are related to local availability of CB1 receptors." https://www.nature.com/articles/s41598-017-14203-4

Would be interested to study if there is a difference in fear response in sober thc users and non-users. Does 'tolerance' of THC entail amygdalar CB1 downregulation? Does this have measurable effects besides intoxication-related anxiety?

---

Anxiogenic effects in rats are greater in adults than adolescents https://www.ncbi.nlm.nih.gov/pubmed/17211649

---

"Guiaol, eucalyptol, γ-terpinene, α-phellandrene, 3-carene, and sabinene hydrate all have significant correlations with decreased anxiolytic activity." (Certain strains may have constituents which increase anxiety - many of these have distinctive smells) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204402/

---

CBD is widely regarded as safe - this study raises some concern. Could chronic CBD use could possible cause upregulation of amygdalar CB1?

Anxiogenic-like effects of chronic cannabidiol administration in rats https://www.researchgate.net/publication/51798464_Anxiogenic...


Depends on whether you are smoking a sativa or indica, and what kind of activity you are involved in? Are you smoking alone or in a group setting. If you are smoking alone and have an anxious personality, I would rather smoke a Sativa strain with a higher CBD to THC ratio. Indicas sometimes take me to an anxious place, but it depends on my mental state before taking the drug. So much of it is setting ( great music, good company ), can make it all the more better.


> Depends on whether you are smoking a sativa or indica

People really need to stop repeating this. There are pure cbd sativas just as there are pure cbd indicas. There is no definition for what a sativa/indica is besides what the leaves look like. There's no bearing on subjective high and strains. What people are experiencing is differing THC/CBD ratios.


You need to stop incorrectly correcting people. CBD is neither sativa or indica. Which strain CBD comes from doesn't change how it effects you.

All of the indica and sativa flower that I purchase is 0% CBD, yet I can most definitely tell the difference. It has nothing to do with the amount of CBD in it.


Your subjective n=1 sample of "I can feel the difference bro" doesn't really mean much to me, especially when it seems like you haven't even really grasped my argument.


Interesting, I was wondering about the paranoia and anxiety comments. Outside of once sharing a blunt and once trying a vaporizer, 2-3 drags on a joint was the maximum of weed I ever took and I never experienced anxiety from it.


The less you use, the more your body will become sensitive to the smaller amounts of it. Meaning, if you dose correctly, you can actually use less to achieve more.

So yep, dosage is extremely critical with THC.


> The less you use, the more your body will become sensitive to the smaller amounts of it.

Do you have any reference to back that up? I ask because I am genuinely curious. I haven't heard this before, and usually with most other drugs the opposite happens, i.e. you slowly build a tolerance that requires taking higher does to acheive the same effects.


Tobacco is very good at clearing things from the body, like drugs or caffeine. Smokers clear caffeine faster from the brain than non smokers.

Check out the P450 group of enzymes to find out how this works, part of the clearance rate is controlled by the liver becoming more efficient and altering your food and drink cravings.

Other foods/chemicals like grapefruit juice slow the metabolism of some drugs, so 2litres of grapefruit juice combined with 50Mg of viagra will see you visiting A&E with a 5hr priaprism, that has to be let down with andrenaline injections into the corpus spongiosum.

Generally if you want your illegal drugs to last longer dont smoke.


It wasn't until things were legalized that I had the option to try a 1:1 strain (equal ratio of CBD to THC) and I've found that to be a much better balance for me. The psychoactive aspects are still there, but less intense, more relaxing and without negative feelings. Kind of like sipping beer vs shooting tequila.


This is a perfect example of how prohibition doesn't work. When alcohol was illegal in the USA, the only drinks you could really get a hold of was whiskey, moonshine and other high percentage beverages.

When illegal, the dealers want to be the ones with the best (strongest) product on the market.

Once made legal, the lower percentage drinks became available such as wine and beer, and they became the best selling and most popular type of drink. Drink that doesn't smash them across the face by the end of the night.

The same will (and is) true in regards to weed legalisation, the powers that be will harp on about weed these days being too strong, and shouldn't be legalised for that very reason, yet it has been shown that stronger drugs is an effect of a ban on the sale of these products.

The sooner it is legalised, the better, as I will be able to go to a shop and have all the available information at hand to help me make the best decision for my anxiety requirements. Instead, atm, I have to go to a dealer, who sells all the finest buds, but I have nothing to go on other than look, smell, and anecdotal evidence from someone who's main purpose is sell all her flowers, not ensure her customer is getting the right product for her needs.


This is the most exciting thing about legalization to me. If I could go buy high cbd strains with a manageable level of thc I’d be first in line. I don’t want to get super high on thc. I just want all of the other effects.


They definitely sell 10:1 CBD:THC and 100% CBD in California. 100% CBD weed doesn’t even need to be sold at dispensaries. They sell that at lots of stores. My mom said the feed store has CBD oil for your pets.

Legalization is the best.


CBD is "technically" federally legal since the 2018 Farm Bill. Practically, it's in this limbo position where if it's allowed without any restrictions it's very hard to control THC which is a Sched 1 drug that Feds care a lot about. That's why even though you can buy CBD from your closest market, people still get busted for "smuggling" because CBD cannabis (and hemp) looks identical to marijuana. So currently it's in this weird limbo state where it's 100% legal but its legality cannot be enforced so in some places it's not possible to find CBD.

Also, I think CBD is effective for dogs and cats (e.g. for seizures) but apparently there is some evidence THC is toxic to cats and dogs. So PLEASE be sure your CBD doesn't include THC before feeding it to your pet.


yes, its technically federally legal, but some cities around me are still prosecuting CBD possession


Less THC in the leaves, more CBD in the leaves.


Not a stupid question. Stigma around the plant has created this vacuum of pop-culture knowledge on this sort of thing.

Over a hundred different cannabinoids have been identified. CBD is a cannabinoid, and so is THC. THC is what makes you high. CBD does not.

You really need to get high with a scientist who has a ton of experience with weed. Then you can actually try different things, knowing what you are ingesting and using different methods, too (like vaporizing oil vs. smoking a flower)

Check this out to learn more about all the different cannabinoid's that we know about: https://en.wikipedia.org/wiki/Cannabinoid

Final thing to add would be to take a look at this picture: https://blogodiversity.files.wordpress.com/2012/09/dogs_of_t... and then think about all of your various experiences with dogs throughout your life. Dogs are all dogs, but they are TOTALLY different across breeds and even within breeds. The same applies to Marijuana... you will enjoy or dislike the characteristics of certain strains the same way you might like or dislike a dog or cat.


I've never been able to tolerate marijuana and have been around recreational users all my life. It's always caused me extreme anxiety. In the past year, I've experimented with various CBD products for chronic pain.

I've had mixed results for the pain, but the CBD definitely produces an anti-anxiety and a relaxing effect with none of the negative effects that I associate with marijuana, presumably with a great deal more THC.


Anecdotally, it depends on the person.

Marijuana makes it easy for my over-worrying brain to relax and trust that things will turn out okay. Other people I know find the opposite.

Edit: this is also a study of CBD specifically, not of weed as a whole.


To summarize a bit unnuanced:

THC induces paranoia

CBD reduces it

The ratio is an important one between them as it alters the experience a lot.

Weed is a bit like love, the term is convoluted and overloaded.

E.g.

Dutch weed: HIGH in THC! Normal in CBD. Oh dear, the Dutchies... Sigh

Swiss weed: high in CBD, extremely low in THC

The experience? Completely different.

Sources (cannot Google search atm, am on mobile):

- I am Dutch, and am well acquainted w/ Dutch weed

- In Switzerland they sell weed in cigar shops and they have labels on THC and CBD levels.


More or less my experience as well, stuff I go for regularly are 13-15% THC to 1% CBD. Depending on where you get your weed from, coffeeshops do occasionally mark their ratios.

I should probably go for higher CBD ones...


I smoke THC distillate with essentially no CBD, I find it to be calming and not to induce anxiety or paranoia.


That's possible, for some it does nothing, for others it can be the path to non-recoverable schizophrenia. My advice to people who smoke high THC is: if you have had weed-induced psychosis then you might be able to develop schizophrenia with prolonged use of high THC weed. In other words: smoke seldomly.

However, it might also be possible that one simply doesn't notice their cognitive decline. To check on this, people would need to listen carefully to their environment. If they say something is wrong with you, then something is probably not right indeed.

The reason for this is: schizophrenia and psychosis related phenomenon take away the ability to self-reflect.

Unfortunately, I don't have sources for this, other than that I read up on it. But for now, it simply is just one opinion on the internet. Search engines are your friend here, especially academic search engines. And I have friends who are psychiatrists, so those conversations help.


there are two major active components in cannibis: THC and CBD. THC is generally responsible for the “high” and also for tendency for anxiety in some people. CBD is though to give the “mellow” feelings and to have anti-inflammatory properties. A give strain of Cannibis will have different proportions of the two and different people will react more strongly to one or the other producing varied results. CBD is often extracted and use for calming and anti-inflammation.


This is for CBD. Anxiety from cannabis is typically attributed to the THC content.


Probably depends on the person, strain, and frequency of usage... for me it melted away stress and helped me sleep.

I used it pretty sparingly though.


From my experience and own research it's highly dependent on the ratio of THC to CBD (there are over one hundred cannabanoids in the plant which have the desired benefits, but for simplicity sake just these two are used in general discussion). I found when I have recently experienced, or have underlying feelings of general anxiety, high THC strains make the anxiety worse, ruminating thoughts become unbearable. The more you take the worse this feeling gets. (Edibles can be a horrible experience in this state)

Essentially it depends on your predisposition to anxiety, the dosage you take, and the ratio of THC to CBD.

Balanced ratios that would make this much less likely and induce a more relaxed or energetic state depending on the more dominant chemical. Unfortunately the legality of it makes it impossible to verify the ratios of cannabis substances


> I hear Cannabis is used for anxiety relief but doesn’t smoking marijuana induce anxiety?

This is, as I understand, dose, strain (apparently, largely CBD/THC relationship), and user (anecdotally, I've heard reports of basically reverse the more common relative effect of different strains from people on the autism spectrum, along other variations).

Even for single drugs that don't have issues like the CBD/THC one, there are lots that have dose dependent (not just more with higher doses, but switching at some threshold) and/or user dependent effects like that.


I'm anonymous on HN so I can tell you that some people go out of their way to grow special strains that have more CBD in them than they do THC.

One such strain I have experience with is CBD Kush and I know for a fact that it has helped someone with ADHD.

CHD Kush is supposed to have an equal amount of CBD and THC but is very easy to grow and get a good yield like 50-60g dry per plant.

But there are other strains out there I'd love to try like Charlotte's Web which is the most famous example.

People tend to maximize the THC because it's psychoactive but it also makes people anxious.


From my layman's understanding of it: cannabis lowers blood sugar, and low blood sugar can trigger the release of adrenaline, and that fight or flight feeling combined with inhibited short term memory can be stressful. For people who are susceptible to psychosis, this can trigger a psychotic state.

If you're having a bad time after smoking, get your blood sugar up.


One more factor, besides the ones other posters have pointed out, is tolerance. I find my tolerance to the anxiety provoking effects increases faster than my tolerance to the anxiolytic effects. If I haven't consumed any in a while, I find I can get that initial panic. Ride it out though and the more relaxing effects take over.


A few personal anecdotes:

Sativa has a stronger anxiety producing effect for me than Indica if I remember correctly. I really only smoke sativa. That said, some sativa strains produce more anxiety than others. But when I do experience marijuana-induced anxiety, it tends to be very near the beginning of the high and subsides pretty quickly.


Just the opposite for me. I find Sativa to generally lift my mood. I'm more likely to be social, carry on conversations and have interesting thoughts. Compared to Indica, which for me has more of a lazy effect. That may be great for serious pain management, but if I'm laid up my mind is more likely to go in different directions.


The mood lifting effects happen with sativa for me too. But if I happen to feel anxiety from it, it will be a short lived bit at the beginning.


Part of this phenomenon is likely that thc heavy strains have been selected for over time (at the expense of cbd) because people valued the “potency” of the flower.

Another major aspect is that weed has been illegal for most of its modern usage, and the fact that people are doing something illegal/dangerous adds to the anxiety.


Here's one possible vector... Intoxicants in general make people overconfident. If you get to doubting — with good reason — whether you're actually as entertaining and creative as you feel, that'll make you anxious.


A friend had an explanation for this, and I really agreed with him. The antianxiety effects of THC arrive after the initial high. The beginning is a spike of feelings that a lot of people find to be intense... and leads to paranoia and an increase in anxiety. But as this brief rush fades there is relief and a longer lasting calm.

To put it another way: after a stone is dropped in a pond the splash is a mess, but the ripples that follow sure are pretty. :)


Interestingly marijuana does make me feel anxious, but at the same time completely alleviates my social anxiety.


The logic is that CBD is different than THC, the anxiety provoking, psychoactive chemical.


Why I post this: I am trying to sleep but can’t (on my phone to not wake anyone). I was wondering whether CBD might help.

The study is simply a discussion prompt.

My query also found [1]. I wonder who else has some insight into CBD.

Edit: since this comment is quite down the discussion thread I would like to promote another topic [2]. It is about creating wearables that are able to measure stress. Measuring stress [2] and controlling stress (this topic) are underlooked things, in my opinion.

[1] https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-...

[2] https://news.ycombinator.com/item?id=20340989


I’ve had chronic insomnia for over 3 years. The day I started CBD, was about 4 months ago. Right before that, my option was to try Ambien that I had to pry off from the doctors hands. I’ve not had the guts to try it after hearing it messes with your brain and causes you to have suicidal thoughts.

So I tried CBD after a quick research. First night, I didn’t feel a difference. I did feel a bit sleepier but I thought that was just my mind wanting to think that way. But after weeks of using it, I now can notice a calming effect that happens within 30 mins to an hour. And after I sleep, I wake up actually feeling refreshed. Some nights, I feel like I slept for days. It various night to night.

But compared to when I did not take CBd, I am sleeping way better now with cbd. I used to be on the fence about it’s effectiveness but the effects are so noticeable to me now that I’m incredibly thankful for CBD.

And for those that say just take a puff of the real thing, I never got a good night sleep with thc, I may get knocked out but I feel tired waking up. On the contrary, CBD actually increases your deep sleep cycle where as THC shortens it, similar to Ambien. This is a big factor you can’t ignore.


Where have you read that CBD increases the amount of deep sleep? I have looked into this quite extensively, and never found any information that suggested that.


Joe Rogan https://youtu.be/Pjeb9kOSJ2M

I think it was this but it could’ve also been some online article.


It would have been nice if he would have included a citation for that claim. I have wanted this to be true for a long time!


Joe Rogan is not a primary source.


What method did you take cbd (pill, etc..)?


It was the tinctures


Why don't you try it for yourself? In my experience the effects are very mild, but does seem to help silence that "internal chatter" which causes anxiety and prevents one from getting to sleep.

I've also found turning off all you devices ~2 hours before bed and reading a book until my eyes get tired to be of even greater help with getting to sleep quickly and feeling well rested the next day.


This is definitely anecdotal, but I also have a hard time getting to sleep. I tried CBD just on a whim to see if how it would affect me. I didn't really read up on it's affects, I was just curious. The only thing I noticed was when I laid in bed at night, I fell asleep super quickly.



Interesting to see an actual study, even if it’s a small test group.

I’m usually getting maybe 4-5 hours of sleep a night, so about 6 months ago I started taking CBD oil at night (500mg and then 1500mg hemplucid). My experiences are pretty consistent with the study results here - I’d get about 1-1.5 hours more a night for the first month, but by month two I was already graduating to the 1500mg strength because my body was adapting to it so fast.

By the fourth month I was taking double the dosage of the prior month, and by month six I stopped taking it altogether… the effects were severely diminished and at $200 a bottle for the 1500mg strength, it would be more cost effective to just smoke the real thing as it is now legal where I live.


I think you may have actually been medicating for the CBD side effect. I found when I started taking CBD that it helped a lot with anxiety but made me a little drowsy and helped my sleep somewhat. Over the next week or two the drowsiness mostly went away and my sleep was back to normal but it still helped with anxiety.

Unless your poor sleep is driven by anxiety, CBD is probably not the best choice. Some strain of Indica pot is probably what you are looking for.


I had the same 4-5 hours sleep issue until I started to exercise/run regularly. Being a recovering addict/alcoholic, I usually avoid any dependencies, which is why I can't start taking a substance, even if it helps with sleep. In any case, are you getting regular exercise?


I exercise pretty heavily. it's a different thing entirely.


Exercise was the answer for me as well.

I usually run in the morning, but switching to evenings proved more effective for sleeping longer.


jesus that's pricey. Was gonna say, why not just take a puff of the joint at the end of the day?


It can sometimes be tough being married and starting a habit like that when your spouse doesn’t partake often.

Yes, smoking is more effective than CBD, but exercise won out eventually.


The cbd feeling for me is that the breathing gets slower and heavier.

This was something I thought you obtain through meditation or other calming exercises but cbd just provides you this feeling within 30 mins.

It’s especially nice after sleep. Because it’s those times when you wake up and your breathing have slowed to the point it relaxes you on each breath you know you had a rejuvenating sleep.


FYI I got my CBD from Apothio.net, they seem to have the highest concentration of terpenes which is key to its effectiveness


> The final sample consisted of 72 adults presenting with primary concerns of anxiety (n = 47) or poor sleep (n = 25).

72 adults seems a bit low to me. Does anyone knows if it's indeed low or a pretty normal sample for that kind of study?

Besides, this study does not seem placebo-proof, right?


It's not a study. It's a post-facto case series, meaning they looked at some users who were given CBD and see how they responded. There was no control group.

In other words, certainly raises interest to do an actual study, but absolutely 0 other conclusions can be drawn from this report.


Small study with mostly small doses and better than expected outcomes IMHO.

I have several friends using CBD for anxiety and depression (in addition to normal meds.)

IMHO, it has profound potential medically. Anecdotal evidence is unreliable, but one close friend of mine started taking doses at my insistence while going through cocaine and heroine withdrawal. It make a profoundly noticeable change in her attitude.

I hope that more clinical studies are funded regarding it's use for those matters because a cheap and readily available medicine to help with these symptoms is severely needed to help those seeking to end their addictions would be greatly beneficial to society at large.


I have the same hope, which is why I posted this. Moreover, I emailed the first author so they would be aware of the discussion here.


I haven't tried just CBD for sleep, but a few years back I couldn't fall asleep to save my life. A friend suggested smoking cannabis to help, and when I would I had the best sleep of my life.


You had the best sleep experience of your life. That doesn't translate to the healthiest sleep of your life. You were just very unconscious.

THC is well documented for the unhealthy effects it has on your sleep cycles.


I'm sure it was healthier than the 2-3 hours of sleep I was running on before.


Try 7.5mg of remeron/mirtazapine next time.


CBN is supposed to be used for sleep


"One of CBN’s biggest benefits is that it’s a strong sedative, making it effective as a sleep aid and anti-anxiety drug". Here's a writeup about the difference in CBN vs CBD - https://ministryofhemp.com/blog/cbd-vs-cbn/


Probably need to repeat this study with 72 additional individuals treated with a placebo to compare against the cannabidiol group. My guess is that just thinking that you are doing something about your anxiety and sleep issues will result in decreased anxiety.


I'd agree. Brains are surprisingly complicated and dumb.

I carry around anxiety medication prescribed by my doc, but... just the effect of having something that someone tells me will prevent an all out panic is enough that I've never actually needed to take one. The magic isn't powerful enough to make the core problem go away, but it is pretty good at giving me another tool to control it.


Anecdotally this study confirms what I already found out on my own, CBD capsules helps my body relax with none of the anxiety that THC can trigger.

No doubt other people are having the same realizations, CBD capsule prices have gone through the roof.


I've never used THC other than smoking or two or three times in my adult life. Tried CBD for a while and honestly could not feel a thing. Felt like I was taking vitamins.


You can try the experiment on yourself. Find capsules of flax seed oil that look like capsules of CBD oil. Have someone place a one-to-three week supply of each in separate envelopes and take them twice daily. Score your anxiety level each morning until all the tabs are gone. Estimate your average anxiety level each week. Then ask the person to reveal the envelopes to you and see if you can find a measurable difference between the treatments.


To be really sure it would be a good idea to have one person enclose the tablets in the envelopes and a different person to administer them to you.

But I suspect that there might be other factors here that might influence your study design. Mostly because neurotransmitters are super complicated.




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