We are cannabis scientists and experts, specialising in psychopharmacology (human behaviour), neuroscience, chemistry and drug policy. Cannabis use is more popular than ever, and we are here to clear the smoke. Ask us anything!

What are the effects of marijuana use upon the lungs? I’ve always heard that it’s “less bad than tobacco” but are we talking potentially negligible effects, or like “you’re 1% less like to get cancer, but you’re still getting cancer”.

Smoking anything is bad for your lungs. Vaping is better than smoking. Edibles are better than vaping (for your lungs). We don't really know enough about its effects on cancer/lung cancer. Cannabinoids seem to have some anti-cancer properties in controlled lab experiments but the real-world implications are unknown.

I'd also like to know. Are bongs safer to use for lung health?

No. Water pipes are not any less harmful than smoking a joint or a pipe of herbal cannabis. Vaporisation is the least harmful way to administer herbal cannabis by inhalation.

Do terpenes actually have an impact on the quality of the "high" when ingesting cannabis? If so what is the mechanism by which this is happening and what is special about the terpenes found in cannabis compared to the terpenes we find in other sources such as food?

My other question would be if you think there are any lesser known cannabinoids or other compounds that are interesting and may play a role in how we experience the effects of cannabis.

Thank you!

At the molecular level in cellular models, there is currently no evidence that terpenes modulate the activity of phytocannabinoids (including THC) at any receptors--including the cannabinoid type 1 receptor (CB1) responsible for the psychoactive effects of THC. It is hypothetically possible that terpenes act on olfactory G protein-coupled receptors (GPCRs) to modulate some aspects of the cannabis experience, but this has not been demonstrated. Beer contains lots of terpenes (from hops), and these mainly alter aroma and flavour.

There are more than 30,000 different terpenes in nature. Those found in cannabis are no different than the same terpenes found in other sources (foods, beer, fragrances, etc.), and all of the major terpenes found in cannabis are also found abundantly elsewhere.

One way in which terpenes and other lesser-known cannabinoids might be modulating the cannabis experience is by altering that activity of metabolic enzymes that process THC. Again, this would not be expected to have a major effect on the perceived, subjective experience of cannabis intoxication.

Aside from THC (and a few analogues and homologues that occur in tiny quantities), there are no other compounds in cannabis that are known to cause intoxication. Perceived differences in intoxication from different strains of cannabis are very much likely due to power of suggestion and the human mind.

I would love to do a blinded, placebo-controlled study looking at the power of suggestion in perceived effects of cannabis use! I suspect marketing of strains play an enormous role, just as it does with the perceived experience of wine and whisky!

*I should clarify that the effects above are for terpenes at the levels found in cannabis. Terpenes at very high concentrations (like in essential oils and other extracts) have shown limited evidence of biological activity.

I’m a medical user in Canada. There is NO WAY that terpenes don’t alter a high. I use certain strains to treat different health problems because their effects are so different, even when lab tested and shown to be very close in THC/CBD levels.

Terpenes may be effecting the high. It is possible but it has been very difficult to demonstrate scientifically. It is also possible that there are other phytocannabinoids in there that could be influencing the high, or other plant compounds, or your subjective experience of the different cannabis strains.

Has any real progress been made developing roadside tests that are verifiable by cameras or other means of establishing active intoxication than blood tests?

I was charged with a DUI, with no faults visible on my field sobriety test, and without having smoked that day. I did however have a large amount of THC in my system from the previous month, so I plead out to avoid court hassle.

I was pretty much dead sober when pulled over, and have stopped driving to avoid this BS and expense.

No, I'm afraid no real progress has been made. This is a big problem and something we are trying to work towards.

I'm curious about this one - where you are located? So you were pulled over, passed a field sobriety test, but then had to provide a blood sample anyway?

Thanks for the response, its a shame to hear about the lack of progress.

I was in Texas responding to a family health crisis, but lived in Oregon and had a medical card. I agreed to the FST, because I had only consumed one beer a few hours earlier. I know now this was probably a mistake.

I passed all of the FST that can be corroborated with video, but supposedly failed it due to eye testing that were not recorded. The officers word about suspicious eye movements was enough to fail the FST and force a blood sample.

Refusing the blood sample would have led to a loss of my drivers license for 9 months. I probably should have gone with that option but relied on my car for both work and college. I ended up pleading out to Obstructing a Public Passageway, but still had to pay the state thousands.

I quit driving because I realized I could be charged with a felony at an officers discretion and without verifiable evidence.

I just did a bit of reading about the laws in Texas. Looks like they don't have a per se blood THC limit there, so you would most likely have been charged with driving while intoxicated due to failing to the eye movement test rather than due to having THC in your blood. Sounds like a complicated one, and I don't have enough information or legal expertise to give you a good answer here.

Stay safe, and avoid driving while high or if you have recently use cannabis.

You may our recent publication here interesting:

https://www.tandfonline.com/doi/abs/10.1080/15389588.2020.1851685?journalCode=gcpi20#metrics-content

Hi

A lot of people claim that weed helps them fall asleep. My experience is quite the opposite, no matter if its sativa or indica strains consumed. I have a very hard tme falling asleep at night if I smoked weed up to 6 hours or so before. Is there an explanation why people feel so differently about this? Also, why do people dream less when they smoke or could it just be that their memory of it is worse?I am interested in all aspects of cannabis and sleep, as for me, it is the one big negative thing about smoking weed.

Hard to say why some people respond differently to cannabis when it comes to sleep. This is true for lots of drugs - some people just don't respond the way that most people do. Some sedating histamines, for example, will knock one person out but keep another person awake. THC does decrease the amount of time spent in the phase of sleep known as REM, which is when dreaming tends to occur. So that goes some way to explaining that. But to be honest - we don't know much about this. Another alternative explanation is that cannabis impairs memory formation - so it may be that you are still dreaming but that you just don't remember what you dreamt about in the morning very well.

The alternative explanation is interesting. Anecdotally I’ve heard from a number of former long term, chronic smokers that they experienced a lot more dreams and more vivid dreams upon quitting.

I've heard this too.

Cannabis strains in the US are certainly more potent than stuff I've tried in India and smoking a full joint typically sets me off on a paranoia spiral. I'd like to understand what the current consensus in the field is, about the effect on THC on the amygdala as it relates to symptoms of anxiety. I presume that cannabis can reduce anxiety but mostly when used in moderation. So, is there a sweet spot in terms of dosage, and at a molecular level, is there really a difference (as touted) between the strains e.g. sativa, indica etc? Any related research paper links would be great.

It is well established that THC can produce anxiety, with higher doses of THC causing high levels of anxiety. Many of the strains you can find now in the US and Canada are, as you say, far higher in THC than most cannabis you would typically find growing wild in India or Nepal or in Morocco - i.e. mountainous areas where cannabis grows as a 'weed'. They have been bred to be like this, and it is an interesting question what effect using such THC-rich products will have on long-term cannabis users.

Cannabis is cannabis, and the whole sativa indica thing is just about plant genetics. The reality is that most strains now have been so cross-bred over time that the sativa/indica distinction is essentially unhelpful and misleading.

There are lots of interesting papers in this space - try this one for starters: https://www.liebertpub.com/doi/full/10.1089/can.2016.0017

Hey. Thanks for taking to time to do the AMA.

Can you expand a bit on why sativa and indica distinction is unhelpful? I consume cannabis and I usually get the expected effects from a sativa strain and indica, and would say I do find it helpful to know before I smoke a strain roughly what type of effects to expect.

Different strains of cannabis may produce different effects because of their chemical composition. But the botanical classification of 'indica' and 'sativa' are not related to the chemical composition of cannabis plant. Indica and sativa describe how the cannabis plant looks, and they do not describe the cannabinoid profile of the plant. However, it's very common for people to experience indica and sativa differently because people expect to experience them differently. In the same way that some people say 'oh, drinking gin makes me sleepy but whisky wakes me up', when really it's all just alcohol. But the expectation ends up causing the effect.

If someone has used cannabis and stimulants to self-medicate their ADD, depression and anxiety from ages 16-27, what cognitive struggles would you expect them to face in kicking that habit? Has the brain formed around those substances?

You will likely find that it takes a while for you to find a new 'normal', so hang in there and do all the things you can do to look after yourself (e,g. eating well, sleeping well, exercising). You might find it hard to sleep for a while, you may find yourself moody or irritable, but over time, you will find your short term memory improves and you may feel more focused or clear-headed in your daily life.

If someone has used cannabis and stimulants to self-medicate their ADD, depression and anxiety from ages 16-27, what cognitive struggles would you expect them to face in kicking that habit?

The brain is developing in response to everything it is exposed to and will develop accordingly. But in saying that, it does remain "plastic" (malleable) so you can 'teach an old dog new tricks' or kick old and ingrained habits.

Cannabis itself does not cause physical dependence but you can get addicted to the sensations. Stimulants can cause physical dependence, which may make it a bit more challenging to stop but not impossible.

There's a lot of research being conducted on substance use disorders, e.g. psychedelic-assisted psycotherapy. Interestingly, CBD itself is also being investigated as a candidate and showing promise.

I have a family history of schizophrenia. Can you talk about the link between schizophrenia and THC?

General advice is to avoid cannabis altogether if you know you have a family history of schizophrenia. Cannabis can lead to serious long-term ill effects in individuals who are predisposed to schizophrenia and other psychiatric disorders.

Even without showing symptoms after 38 years?

Even without showing symptoms after 38 years. It's a risk that some people may be willing to take, but any medical professional would advise that you avoid it altogether.

How does vaporizing cannabis affect lung health?

We don't have enough long-term data on this yet. Vaping is a relatively recent phenomenon, and it will likely be decades yet before we have high quality data on how vaping effects long-term lung health. Inhaling anything other than air can be damaging for the lungs, but from what we know, vaping seems to be a much safer alternative to smoking due to the absence of toxic byproducts that form when plant material is burned.

I have Crohn’s diseases, is there any promising studies I can read up on? I currently use cannabis instead of Zofran and Vicodin for my pain and nausea. Any suggestions of strains effective for my illness?

Here are a couple reviews on the topic. If you can't access them, send me a message and I'll email them through.

Cannabis for the treatment of Crohn's disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517156/

Abstract

Background: Crohn's disease (CD) is a chronic immune-mediated condition of transmural inflammation in the gastrointestinal tract, associated with significant morbidity and decreased quality of life. The endocannabinoid system provides a potential therapeutic target for cannabis and cannabinoids and animal models have shown benefit in decreasing inflammation. However, there is also evidence to suggest transient adverse events such as weakness, dizziness and diarrhea, and an increased risk of surgery in people with CD who use cannabis.

Objectives: The objectives were to assess the efficacy and safety of cannabis and cannabinoids for induction and maintenance of remission in people with CD.

Search methods: We searched MEDLINE, Embase, AMED, PsychINFO, the Cochrane IBD Group Specialized Register, CENTRAL, ClinicalTrials.Gov, and the European Clinical Trials Register up to 17 October 2018. We searched conference abstracts, references and we also contacted researchers in this field for upcoming publications.

Selection criteria: Randomized controlled trials comparing any form of cannabis or its cannabinoid derivatives (natural or synthetic) to placebo or an active therapy for adults with Crohn's disease were included.

Data collection and analysis: Two authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. The primary outcomes were clinical remission and relapse. Remission is commonly defined as a Crohn's disease activity index (CDAI) of < 150. Relapse is defined as a CDAI > 150. Secondary outcomes included clinical response, endoscopic remission, endoscopic improvement, histological improvement, quality of life, C-reactive protein (CRP) and fecal calprotectin measurements, adverse events (AEs), serious AEs, withdrawal due to AEs, and cannabis dependence and withdrawal effects. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) and 95% CI. Data were combined for analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). Data were analyzed on an intention-to-treat basis and the overall certainty of the evidence supporting the outcomes was evaluated using the GRADE criteria.

Main results: Three studies (93 participants) that assessed cannabis in people with active CD met the inclusion criteria. One ongoing study was also identified. Participants in two of the studies were adults with active Crohn's disease who had failed at least one medical treatment. The inclusion criteria for the third study were unclear. No studies that assessed cannabis therapy in quiescent CD were identified. The studies were not pooled due to differences in the interventional drug.One small study (N = 21) compared eight weeks of treatment with cannabis cigarettes containing 115 mg of D9-tetrahydrocannabinol (THC) to placebo cigarettes containing cannabis with the THC removed in participants with active CD. This study was rated as high risk of bias for blinding and other bias (cannabis participants were older than placebo). The effects of cannabis on clinical remission were unclear. Forty-five per cent (5/11) of the cannabis group achieved clinical remission compared with 10% (1/10) of the placebo group (RR 4.55, 95% CI 0.63 to 32.56; very low certainty evidence). A difference was observed in clinical response (decrease in CDAI score of >100 points) rates. Ninety-one per cent (10/11) of the cannabis group achieved a clinical response compared to 40% (4/10) of the placebo group (RR 2.27, 95% CI 1.04 to 4.97; very low certainty evidence). More AEs were observed in the cannabis cigarette group compared to placebo (RR 4.09, 95% CI 1.15 to 14.57; very low certainty evidence). These AEs were considered to be mild in nature and included sleepiness, nausea, difficulty with concentration, memory loss, confusion and dizziness. This study did not report on serious AEs or withdrawal due to AEs.One small study (N = 22) compared cannabis oil (5% cannabidiol) to placebo oil in people with active CD. This study was rated as high risk of bias for other bias (cannabis participants were more likely than placebo participants to be smokers). There was no difference in clinical remission rates. Forty per cent (4/10) of cannabis oil participants achieved remission at 8 weeks compared to 33% (3/9) of the placebo participants (RR 1.20, 95% CI 0.36 to 3.97; very low certainty evidence). There was no difference in the proportion of participants who had a serious adverse event. Ten per cent (1/10) of participants in the cannabis oil group had a serious adverse event compared to 11% (1/9) of placebo participants (RR 0.90, 95% CI 0.07 to 12.38, very low certainty evidence). Both serious AEs were worsening Crohn's disease that required rescue intervention. This study did not report on clinical response, CRP, quality of life or withdrawal due to AEs.One small study (N= 50) compared cannabis oil (15% cannabidiol and 4% THC) to placebo in participants with active CD. This study was rated as low risk of bias. Differences in CDAI and quality of life scores measured by the SF-36 instrument were observed. The mean quality of life score after 8 weeks of treatment was 96.3 in the cannabis oil group compared to 79.9 in the placebo group (MD 16.40, 95% CI 5.72 to 27.08, low certainty evidence). After 8 weeks of treatment, the mean CDAI score was118.6 in the cannabis oil group compared to 212.6 in the placebo group (MD -94.00, 95%CI -148.86 to -39.14, low certainty evidence). This study did not report on clinical remission, clinical response, CRP or AEs.

Authors' conclusions: The effects of cannabis and cannabis oil on Crohn's disease are uncertain. Thus no firm conclusions regarding the efficacy and safety of cannabis and cannabis oil in adults with active Crohn's disease can be drawn. The effects of cannabis or cannabis oil in quiescent Crohn's disease have not been investigated. Further studies with larger numbers of participants are required to assess the potential benefits and harms of cannabis in Crohn's disease. Future studies should assess the effects of cannabis in people with active and quiescent Crohn's disease. Different doses of cannabis and delivery modalities should be investigated.

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An overview of cannabis based treatment in Crohn's disease: https://www.tandfonline.com/doi/abs/10.1080/17474124.2020.1740590

Abstract

Introduction: Cannabis use among inflammatory bowel disease (IBD) patients is common. There are many studies of various laboratory models demonstrating the anti-inflammatory effect of cannabis, but their translation to human disease is still lacking.Areas covered: The cannabis plant contains many cannabinoids, that activate the endocannabinoid system. The two most abundant phytocannabinoids are the psychoactive Tetrahydrocannabinol (THC), and the (mostly) anti-inflammatory cannabidiol (CBD). Approximately 15% of IBD patients use cannabis to ameliorate disease symptoms. Unfortunately, so far there are only three small placebo controlled study regarding the use of cannabis in active Crohns disease, combining altogether 93 subjects. Two of the studies showed significant clinical improvement but no improvement in markers of inflammation.Expert opinion: Cannabis seems to have a therapeutic potential in IBD. This potential must not be neglected; however, cannabis research is still at a very early stage. The complexity of the plant and the diversity of different cannabis chemovars create an inherent difficulty in cannabis research. We need more studies investigating the effect of the various cannabis compounds. These effects can then be investigated in randomized placebo controlled clinical trials to fully explore the potential of cannabis treatment in IBD.

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We don't really operate in strains. We are focusing on individual cannabinoids to tease out their specific actions. Both THC and CBD have shown efficacy for pain and nausea. We don't really know enough about the other minor cannabinoids just yet.

Same question. Dumbass disease.

:( my sincerest sympathies to you all. Sending low FODMAP hugs

What might be the affects of cannabis for a pregnant woman? Is there a research about the influnce on the baby?

Thanks!

General advice for anyone who is pregnant is to avoid all alcohol and drugs - including cannabis. Cannabis use during pregnancy does appear to be a "risk factor for poor neonatal outcomes" - https://www.mja.com.au/journal/2020/212/11/deleterious-effects-cannabis-during-pregnancy-neonatal-outcomes

what do you guys think about delta 8 thc?

Delta-8-THC is a regioisomer of the more common delta-9-THC...In studies on cannabinoid receptors and in mice, it possesses a similar pharmacological profile to delta-9-THC and might be expected to produce largely similar effects in humans.

There's a lot of argument among regular users in regards to Marijuana impact on depression.

Is Marijuana actually helpful for depression? Why/why not?

Some speculate that the Marijuana eases the anxiety of being overwhelmed by the feelings that are associated with depression. Such as but not limited to hopelessness, sorrow, guilt, regret, etc. So the person can address the depression without being swept away by it. Does this have any basis in reality?

There is growing evidence to support CBD for anxiety but the jury is still out on the use of cannabis for depression.

Our academic director, Prof Iain McGregor appeared on a podcast a few days ago talking about the matter: https://twitter.com/Lambert_Usyd/status/1361831295358148609 I like how he said, ""They're not necessarily going to cure your anxiety or depression but they might give you some breathing space to work out the issues that are affecting your mood and wellbeing." It won't be a quick fix, you still need to put in the hard work (healthy lifestyle, therapy etc) but it might help you get there.

I can understand that for sure. Are there any large scale studies being performed that might give us the smoking gun?

Lots of trials happening for anxiety. Not many for depression... yet.

How long does it take for brain/neuronal connectivity to change with chronic use? Are these changes reversible? Im sure it depends on the amount of usage and many other factors too but any insight is appreciated. Thanks!

There is no clear answer to this one. It depends on how long you have been using cannabis for, and how much you have been using. The brain is remarkable malleable, and most of the changes induced by cannabis are reversible. For most people, a few months is enough to notice significant changes, while for others, it may be a year or longer.

As a long time user of cannabis to help deal with my anxiety and depression and now being forced to be sober due to court related issues (was caught with wax in an illegal state,) I’ve noticed an uptick in my mood swings and increased paranoia. Do you think even after months of quitting it could be psychological withdrawals or would it be more related to my given circumstances? I’ve discussed this with my therapist and she is unsure as well. I’m also curious if self medicating with cannabis daily could be seen as detrimental to mental health. Thank you for all the research you wonderful people have done!

Withdrawal effects can take months to go away, especially if you used cannabis heavily and for a long time prior. Your circumstances do also sound stressful, so I'm sure that isn't helping anything. Give it a few more months and see if you notice any changes. Mental health is a tricky one - cannabis can be both a savior for some and a real trigger for others than can lead to serious, long-term issues.

Some of the best things you can do in your daily life to help with anxiety and depression are eat well, exercise regularly and get plenty of sleep.

A lot of people claim weed is not addictive, or that THC is not an addictive substance.

Would you agree that this is untrue and that weed can actually be addictive?

Also I have had mangos, green tea and dark chocolate 45 minutes before I smoked as I found it boosts my high, is there any other foods/drinks that can boost ones experience?

I think most people would agree that cannabis use can be 'habit-forming', which is really just a nice way of saying addictive. Most people who using cannabis for a long time tend to use more and more over time and experience withdrawal effects when they stop using it. These side effects are mild - e.g. not being able to sleep, mood disturbances - are certainly far less severe than the side effects associated with lots of other drugs, but they still exist. These are some of the criterion that we typically use to define addiction. There are also lots of people who present to treatment because they want to reduce their cannabis use but find it hard to do so. So if you look at this way, I think it is fair to say that THC is an addictive substance. Like everything, it's on a scale. Nicotine, for example, is far more addictive than THC despite its being legal just about everywhere.

As to the mangoes, green tea and dark chocolate - the jury is still out on this one, but current scientific evidence suggests that all this stuff about the synergistic effects of certain terpene rich foods (e.g. mangoes which contain myrcene) and cannabis is unsubstantiated.

Do you think the pharmaceutical model of isolating specific compounds for use in medicines works for cannabis and patients, or is cannabis more effective in general in its more natural form (whether it is flower or a 'natural' extract)? Is there evidence for one approach or another?

This is an interesting question...Lots of people believe that whole-plant extracts are more beneficial than isolated compounds (maybe due to the 'entourage effect'), but there is no good scientific evidence at the moment to support this. From a strictly medical perspective, using a single compound to target a disease makes more sense because there are less variables at play. If someone responds well to a whole plant cannabis extract, you don't know which part of the extract is really producing the beneficial effects which makes it a far less targeted approach. Unfortunately this often gets portrayed as a battle between big pharma and people that believe cannabis is a panacea which is just not helpful in terms of having a productive conversation.

I would like to know more about the application of cannabis in psychiatry for conditions like anxiety, depression, and neuropsychiatric disorders like ADHD/ADD and autism.

I know there's been a few studies on high-CBD/low-THC cannabis and autism, and that some study found differening levels of endocannabinoids in autistics.
I'm autistic (and have ADD) and have found that high-CBD does help in some ways and high-THC/moderate-CBD helps in other ways, are there any studies being planned/done on the effects of high-THC cannabis and autism (and ADHD/ADD)?

high-THC cannabis and autism (and ADHD/ADD)?

Most of the research I have come across is using CBD-dominant products to manage ASD symptoms. As you said, the endocannabinoid system has been shown to be altered in patients with ASD, suggesting that targetting the endocannabinoid system might have therapeutic benefit.

CBD is more desirable compared to THC because it has hardly any side-effects. I think in the case of ASD as well, the treatment plan is targetted more towards children or younger adults, where THC would have potentially more detrimental than beneficial effects.

Are there any contraindications for other medications when smoking cannabis? None of my medication leaflets ever mention it.

THC and CBD do seem to interact with some medications.

"CBD has been reported to interact with anti-epileptic drugs, antidepressants, opioid analgesics, and THC, but surprisingly, it interacts with several other common medications, e.g. acetaminophen, and substances including alcohol." https://link.springer.com/article/10.1007/s11606-020-06504-8#:~:text=As%20expected%2C%20CBD%20has%20been,acetaminophen%2C%20and%20substances%20including%20alcohol.

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This study also has a list of suspected or proven drug-drug interactions: https://www.karger.com/Article/FullText/507998

Just wondering, what are the finding with cannabis use and lifting weights? Does weed kill gains?

Well I don't think using cannabis causes muscle wasting or anything like that, but I did once have a personal trainer who was an ex-MMA fighter and he said he used to smoke weed and then go to the gym and work out for hours without realising how much time had passed. Not that I'd recommend lifting weights while stoned! In fact, a recent literature review found no association between cannabis use and increased exercise performance: https://www.minervamedica.it/en/journals/sports-med-physical-fitness/article.php?cod=R40Y9999N00A20072803

But doing exercise seems to help some people manage their cannabis withdrawal symptoms, here's a recent paper by researchers at the Lambert Initiative: https://onlinelibrary.wiley.com/doi/10.1111/jsr.13211

Are there specific journals or Google scholar alerts you'd recommend keeping an eye on to stay on top of cannabis research?

I've set up research alerts all over the place that I check daily, critically assess, summarise then share on the Lambert Initiative Twitter: https://twitter.com/Lambert_Usyd

It's an easy way to stay up to date with the latest research :)

What are your thoughts on cannabis and epilepsy????

Epilepsy is currently the only indication that CBD has been approved for - this means that CBD has passed the "gold standard" way of assessing drug efficacy. Currently, this is specific to forms of drug-resistant childhood epilepsy (Dravet Syndrome and Lennox-Gastaut Syndrome). CBD is not a first- or second-line of treatment so it is only prescribed after other drugs have failed to work.

Also, just because it works for one form of epilepsy doesn't mean it will work for another -seizures can occur for many reasons. There is research being conducted into other forms of epilepsy at the moment and it will be exciting to see the outcomes.

Regarding THC, there is some evidence suggesting small amounts of THC assist CBD in controlling seizure, while there is other evidence showing THC can be proconvulsant. Again, this could be related to the cause of the seizures being different and therefore respond differently to medication.

One final thing, CBD may have positive impacts on epilepsy patients above seizure-control. CBD might be beneficial to the behavioural symptoms that can commonly occur in epilepsy patients, or ASD patients.

The last time i smoked, I had a bad reaction with some really bad anxiety and a racing pulse. I had never had this happen before. My understanding was that this is not uncommon and is often due to a high THC, low CBD content. Is this accurate, and if so, what sort of amounts/ratio of THC/CBD would one look for to avoid this?

There is evidence to support THC's anxiety-inducing effects. However this seems to be person-specific. Some people never feel anxious while other are sensitive to small amounts. We all have different endocannabinoid systems, that are then constantly changing. THC levels are also increasing in cannabis, so its possible to come across uncomfortably high THC cannabis. The advice that is given to cannabis users is "start low, go slow," which seems to be a good way to operate. Start with no or low THC cannabis and see how you feel, then go from there. If it's not working for you, then stop.

Anxiety and a racing pulse are very common side-effects associated with THC. These things are typically transient and disappear as THC is metabolized into its inactive metabolite, THC-COOH. There is some evidence that consuming CBD with THC can reduce THC-related side-effects, but in our research we've found that this effect is very subtle. Instead of looking at THC/CBD ratios, the best thing to do is simply consume less THC!

hey hey...

i switched to dry herb vaping couple of months ago. with these changes i realized also changes within me. before vaping bud, i mixed the weed with (very) small amounts of tobacco.

now it feels like my memory is much clearer, i dream and have a good dream recall, which is amazing. i also feel that my mood stabilized and cravings(from the tobacco) stopped. most obvious is the state of my lungs/sinuses

the weird downsides:

my facial skin is worse, lots of pimples, overall very sensitive. more mucus builds up and its very thick, snots balls.

do you have any insights why my dream recall is surprisingly good and why my skins and sinuses are so much affected by vaping?

Have other factors in your life also changed? Diet? Amount of exercise? Sleep? Stress?

None of the symptoms you have described above would be expected when switching from a cannabis-tobacco blend to vaporized herbal cannabis (one of the less harmful forms of cannabis administration).

I suspect that some of the changes you have observed may be related to giving up tobacco use, and not smoking anything (cannabis or tobacco).

Do you know much about CHS? I have a dear friend that suffers from it and she also has celiac disease. When she was enduring her symptoms, it almost sounded like gastroparesis to me (especially since she's type 1 diabetic); at one point, she didn't have a bowel movement for around 5 days.

I'm curious, do you think CHS could be a manifestation of underlying gastrointestinal disease? I know the gut is very important and there are tons of serotonin receptors there. Kombucha also seems to be anecdotally helpful for those who have CHS.

This answer is going to be disappointing but we really don't know much about CHS. It is a very bizarre condition.

I was recently revisiting the literature on BIA 10-2474. Given that more than five years have passed since the tragic death and other serious adverse events, I was surprised to find that the mechanism of the toxicity is still not understood and there seems to be little new investigation of BIA 10-2474's pharmacology.

What is the current state of understanding of how BIA 10-2474 exerted its toxic effect? Some hand-waving at non-specific interactions with serine hydrolases that are involved in neuronal lipid metabolism? Am I missing something?

BIA 10-2474

Unfortunately, the mechanism for human toxicity of BIA 10-2474 is not yet understood. It appears to be idiosyncratic for this drug, rather than for its intended mechanism of action (ie, many other FAAH inhibitors have entered clinical trials successfully without similar adverse effects noted).

The selectivity of BIA 10-2474 for FAAH over other serine hydrolases was lower than some other clinical FAAH inhibitors, and the adverse effects occurred at higher doses. Based on our current understanding, you are correct; some hand-waving at likely off-target effects at other serine hydrolases.

The official (and unsatisfying) story from the ANSM Committee found it was likely one of two possible mechanisms, "inhibition of other serine hydrolases, or harmful effects from the imidazole‐pyridine leaving group".

I have scizoaffective disorder bi polar type plus left side brain damage among other problems. I am wondering if its smart to be smoking mass amounts of thc oil. It helps but i do hallucinate. Should i be smoking?

Short answer here - no, you shouldn't be smoking. THC may be doing more harm than good in this case.

Is there proof CBD and or THC products can be used to aide in going to sleep/staying asleep?

The clinical trials that are required to prove the use of cannabinoids in aiding sleep are still being conducted but the early-stage research is showing promise.

I saw a cool review of research come out the other day on this and they had a cool diagram showing how THC affects sleep architecture (the different stages) https://twitter.com/Lambert_Usyd/status/1361413344477933570

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Our research group have also written a good review on this topic: https://www.sciencedirect.com/science/article/abs/pii/S1087079220300824

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And here is a podcast with Anastasia, one of our researchers, discussing the topic: https://sleepjunkies.com/cannabis-sleep-medicine/

I’ve heard that researching cannabis can be challenging because of regulations related to where you can get your research materials from. I know particularly here in the US the cannabis researchers can legally access is far different from what is available at dispensaries. For example as you know labs need to source their cannabis from a federal government source which means there’s a difference between what is being examined and what most people are using, usually the federal government source has significantly lower thc content etc. What implications does this have for research?

That's right - in the US it has been very difficult to conduct research using botanical cannabis. I believe it is comparatively easier to use isolated synthetic compounds, but not certain on that. The US government, through the DEA, has required researchers to only use cannabis grown by the University of Mississippi, which is generally regarded as poor quality. That is starting to change, as the government is allowing new, additional sites to supply cannabis for research. See here for more info: https://cen.acs.org/biological-chemistry/natural-products/Cannabis-research-stalled-federal-inaction/98/i25

In Australia, it's much easier to conduct this kind of research, especially since the 2016 legalisation of medical cannabis. Researchers in Australia do not need to get permission from the Federal government, only a Human Research Ethics Committee. And they are not restricted in the kinds of products they can use (so long as the choice of products is justified, and makes sense for the study).

Regarding drug policy, there's been a small but growing number of educational institutions in the United States offering cannabis 'certificates' with certain disciplines pointing towards agriculture, healthcare, etc.

As experts, do you foresee these certificates or some other form of education being compulsory for entry into a federally legal cannabis industry in the US (or elsewhere around the world)?

I guess it depends on the nature of the specific job, and how the industry matures over time. For example, in other agricultural or biotech industries, having a degree might be an advantage but it might not be mandated as a requirement for a job.

The cannabis certificate educational programs I've come across in the US often appear to be little more than an opportunity to make money. There are lots of people who want to work in the sector, and some people can take advantage of that. Before you fork out money for a course, I would speak with some people in the industry and get their opinion on that specific program first.

Is there any Cannabinoid Oncology research going on at Lambert?

Preclinical? Are human trials legal in Aus?

We have a number of preclinical research programs taking place, looking at the effects of compounds from cannabis on cellular models of melanoma, mesothelioma, and glioblastoma. Others around the world are looking at the effects of cannabis compounds on other forms of cancer too.

We do not have any oncology clinical trials taking place through the Lambert Initiative currently, but such trials are certainly legal in Australia.

So even if the active agents included THC you could do an oncology trial in Australia? wow, that is great.

ive agents included THC you could do an oncology trial in Australia?

THC does have medical benefits, it just also has strong psychoactive effects that can be undesirable.

There is also a THC:CBD study taking place in Australia to treat chemotherapy-induced nausea and vomiting that is showing promising results. "Results of crossover phase II component of randomized placebo-controlled trial evaluating oral THC/cannabis extract for refractory chemotherapy-induced nausea and vomiting (CINV)." https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.12008

Are there known long term effects from smoking? Such as damage to the lungs?

Smoking of any substances is extremely harmful to the lungs. The least harmful ways to ingest cannabis are orally (ie, edibles) or vaporised.

Yes, unfortunately, any form of smoking damaged the lungs.

How would we, lowly citizens, go about getting THC driving laws for prescribed users changed...? (In Australia)

Letters etc to our MPs always seems to fall on deaf ears or lead to empty promises.

Big changes in policy tend to only happen in particular circumstances. The issue needs to be front-of-mind for politicians and the general public and taken seriously as a real issue; it need to be politically attractive for politicians to pursue a policy change; and a viable solution to the policy problem needs to be developed.

I think we're getting to that point with prescribed cannabis and driving. We are reaching a critical mass of prescribed patients who will increasingly start appearing in court to defend against drug driving charges. This will lead to more media coverage and political pressure. Once public support reaches a certain level, it will make sense for politicians to take action. And the action is pretty clear: amend the laws to give equal driving rights to medicinal cannabis patients.

As interested citizens, we can offer to lend a hand to organisations that are coordinating reform efforts such as https://honahlee.com.au/drive-change/

And keep talking about the issue to family and friends!

Good question, and one that we are battling with too!

From my perspective, as a cannabis and driving researcher, what we can do is produce high quality, rigorous scientific studies that will provide the necessary information for law-makers to make sensible, evidence-based laws.

What you can do is just keep on sending letters and calling MPs. It is frustrating and may seem pointless, but these little things do add up, and I am confident that things will start to move in a more sensible direction soon.

If a 16-17 year old smokes weed occasionally (like 1-3 times a month), will it affect their brain drastically long term? I’ve heard that it could because their brains aren’t fully developed yet, but I just want to be sure.

Your brain is still developing until your mid-twenties and your endocannabinoid system is critical for neural development. Using cannabis, which interacts with your endocannabinoid system, will influence your development - and the current evidence suggests that it won't influence it in a positive way.

The current recommendations are to steer away from cannabis until you're older. Probably true for alcohol and other psychoactive substances.

Take care of your brain, you only get one :)

Where do you recommend young scientists who wish to study in your particular field, to go to school?

Start with an undergraduate degree in the sciences, such as a B. Sc., and see where your interests take you! :)

I want to use cannabis but I'm on psych meds. Are you guys making something to make it psych friendly?

Cannabis and psychosis remain a sensitive topic and recommendations would err towards caution.

But there is growing research investigating CBD (with no THC) for the treatment of psychosis and early research suggests that CBD has anti-psychotic effects.

How can thc/CBD used to treat post concussion syndrome and other tbi?

concussion

There isn't too much evidence on THC/CBD for concussion/TBI at the moment. However, based on CBD's anti-inflammatory & neuroprotective actions, it is a potential therapeutic agent that is being investigated!

"Neuroprotection Following Concussion: The Potential Role for Cannabidiol" https://europepmc.org/article/med/32029015

I am interviewing at a lab this week and would be performing HPLC and GC on cannabis samples for my job. My question is - Are HPLC and GC the standard methods for uncovering the secrets surrounding cannabis that we know today? I admire what you guys are doing because I think you are advancing not only the field of medicine but also furthering our collective social understanding of drugs and their prohibition.

HPLC and MS (GC/LCMS) are currently the best methods for analysing all of the compounds found in cannabis.

Thanks for this gang! Can I ask how can we get best results in utilising cannabis use with manual therapies to alleviate chronic (and acute injuries for that matter!) pain. Is there a best combination of THC/CBD for example etc?

There is no 'right' or 'perfect' combination of THC/CBD. It really depends on the person and what works for you. One way you could figure this out is to start with a high CBD product without any THC. If this provides no relief, then try adding in small amounts of THC and go from there. If you are using it medically, then ideally you want maximum therapeutic effects with minimal side-effects, and the best way to achieve this is by using the lowest THC dose possible.

Prob a boring question for you all but interested to hear your answers. Should it be legalised for recreational use and what’s your reasoning? Happy to hear from one or all. Edit f clarity - as in active marijuana

Rhys here - yes, I think recreational cannabis should be legalised because prohibition has caused more harm than good. It hasn't reduced cannabis use or cannabis related harms, but it has made a lot of organised criminals very rich and inflicted immense harms on those who are prosecuted for using it, especially non-white and young people. However, I'm not certain that US-style legalisation is the best way to go. I would like to see Australia start with widespread decriminalisation and not-for-profit social clubs.

Cannabis is less harmful than either alcohol or tobacco, both of which are recreational and legal. The acute of toxicity of cannabis is amongst the lowest of any drug. With proper regulation, the harms of legal, recreational cannabis are very low.

If you had to guess- When do you foresee federal employees being allowed to use cannabis, medically or recreationaly?

In the US, Federal employees will likely only be permitted to use THC-containing cannabis once there has been some kind of national level legalisation. Or until a THC-containing cannabis medicine such as Sativex is approved by the FDA.

In Australia, you are allowed to use prescribed medicinal cannabis and, so long as you are not operating heaving machinery etc., employers should not be able to discriminate against you because of the medicine you are prescribed.

How common is it with spice/k2 in weed? Feels like way to many drugdealers putting in shit like that

I'm not sure how common it is for dealers to mix spice/k2 with cannabis - probably depends on where you live and how available cannabis is. These synthetic cannabinoids are very dangerous and highly toxic.

I have a question for Tom surrounding road safety. We typically think of thc as having a slowing down effect, however I believe I am a better driver while high. I guess it elevates my neuroticism to some degree, but it makes me exceedingly aware of my space bubble and all of the potential things other cars might do. Whereas alcohol can do the opposites. I’m wondering if you’ve found any possible evidence of thc making drivers more alert or aware of their surroundings.?

I often get this response when I tell people what I do! Look, for someone that uses cannabis all the time, knows their dose and is familiar with its effects, their level of driving impairment is likely to be fairly minimal. This does not mean that they will be unimpaired though, and it's highly unlikely that they will be a better driver. The reality is that any drug that has depressant effects on the central nervous system is unlikely to enhance cognitive functions or driving ability. From a research perspective, THC has almost always been shown to reduce alertness, to a greater or lesser extent depending on the population being studied.

hi i am researching the prohibition of marijuana in the US for my final project in high school. I was wondering what your guys’ thoughts are on why it was made illegal and why is it being legalized now? thank you so much for the amazing work you’re doing!! i love it!!

Great question! There were lots of reasons why cannabis was criminalised in the US. Probably most importantly was racism - cannabis was used by Mexican immigrants fleeing the Revolution to the US in the 1910s, that kicked things off. And by the 1930s, the world was dealing with the aftermath of 'the great binge' - from 1900-1930, it was common in Western countries to take cocaine and opium and cannabis for things as benign as a mild headache. So drug control was on the international agenda.

Then of course in the US you had the prohibition on alcohol come to an end, and a powerful agency, the Federal Bureau of Narcotics, suddenly facing irrelevance. This was headed by Anslinger, who championed the racist demonisation of cannabis for personal gain. And he was very effective at doing this. That's the specific context in which the US criminalised cannabis. But since then, cannabis has been caught up in ongoing conflicts between rich white people and poor black/brown people in the US.

I recommend Cannabis: A History by Martin Booth - that's a great book on the subject.

Why is it getting legalised now? Well, partly because of the internet. Prohibitionist propaganda is very effective if there are no other sources of information for people to draw on. The internet really changed that. Also, the medicalisation of cannabis. And in the US, the constitutional referendum systems that some States have allow citizens to initiate ballots, so it got on the agenda there faster than it would have done in Australia, for example.

Phew! This answer could really go on forever, but that's my two cents!

Do you recommend I smoke cannabis?

Do you recommend I smoke every day? (I do)

Smoking is bad for your lungs.

My mother is a patient with fibromyalgia. Can cannabis relieves symptoms?

Evidence is relatively sparse in this area, but a lot of people do report positive effects and pain relief with cannabis. The best thing would be to discuss this with a specialist.

I am a former heavy smoker cannabis only. I quit mostly six months ago and now only stick with edibles and vapes yet after no smoking joints or vaping for a few weeks I ate an edible for past couple days and have gotten a horrible smokers cough. Is it possible that thc triggers my coughing?

It's very unlikely that THC is triggering your cough and much more likely that your body is now just dealing with the effects of heavy smoking.

Will THC shows up during random drug (saliva) test if a non-smoker only consume cannabis leaves and stems only (in form of juice)?

If you are consuming just the raw leaves and stems then most of the THC will be present in its acidic form, THCA, with minor amounts of THC still present. THCA should not cross-react with the assay which is designed to detect THC only. Still - it's very hard to say whether consuming raw cannabis as juice would produce a positive random drug test. It shouldn't, but it depends on the cut-off (the sensitivity) of the test, and the composition of the cannabis.

Hi, I wonder about psychoactivity of edibles. Whole lot of cannabis websites are claiming that edibles are more potent (which I would agree on) and they support this claim by suggesting 11-OH-THC is more psychoactive and, of course, after consumption THC undergoes metabolization to 11-OH-THC. Since I did not manage to find any relevant studies either behaviour or pharmacological (affinity, EC50,etc), I would like to ask what are your thoughts on this topic? Or could it be that smoking is just bad way to consume weed (high temperature, destruction of THC)?

Edibles can be particularly potent because it is easy to consume a lot of THC without realizing you are doing so. The effects also take a lot longer to kick in because THC has to be absorbed through the gut, whereas when you smoke or vaporize, THC is absorbed through the lungs into your bloodstream. This is why people often think they aren't feeling anything so eat more and then an hour or two later suddenly wonder what is happening to the world around them... it's really a question of pharmacokinetics. Smoking/vaporizing is actually a very good way to consume cannabis in one respect because it is easy to titrate the dose (i.e. regulate how much you are having) and the effects come on very rapidly. Smoking anything, of course, comes with its own risks and negatives. Best thing with edibles is to start low (think 5-10 mg THC) and give it a few hours.

Do you think various drugs will be synthesized in the future from specific cannabinoids? For example, synthetically produced CBN, made into a pharmaceutical drug to treat insomnia, much like how CBD has been isolated and produced as a pharmaceutical drug as Epidiolex?

That is entirely possible - in fact, some drugs made from synthetic cannabinoids have been on the market as pharmaceutical medicines for some time, such as Cesamet (nabilone). Although I believe that Epidiolex is derived from plants and is not synthetic. But this single agent medicine approach can co-exist with less pure, botanical cannabis medicines. There are benefits and drawbacks to each.

Edibles and other processed marijuana products generally focus on CBD and/or THC content for therapeutic or psychoactive purposes. Are there other cannabinoids that have significant psychoactive effects and do you think they will become main components of cannabis products in the future? Also on the same point are they any little known cannabinoids that you believe should be talked about more?

There are a lot of possible candidates here! CBN and CBG are both getting quite a bit of attention at the moment. There are a lot of cannabinoids in the plant, and I suspect that many more will be under the spotlight at some point in the future as the cannabinoid of the month, so to speak. I think THC and CBD will remain the focal point for some time though, for their ubiquity in the plant and for the fact that they both do have very clear pharmacological activity that may be medically useful.

I have a question as to what you guys might see FDA approval of cannabis looking like? I see it as falling under a dietary supplement and medicine so I could see it being very confusing. I have a degree in natural science and would eventually like to work my way into that realm and make change. I’m just wondering what you all might think that would look like? Perhaps a more comprehensive label of quantitative lab results paired with qualitative feelings associated (I find skeptic people are unsure how the product is going to make them feel). I just wonder if you may have any insight on that process and if you see FDA approval happening any time soon.

Well first of all, we need to clarify what we mean by FDA approval. For example, the FDA recently approved Epidiolex as a medicine, so that can now be prescribed to patients in the US like any other medicine. That's the traditional, pharmaceutical drug type of FDA approval.

But I get the feeling you're actually asking about broader CBD/cannabis regulation at the federal level in the US. And that's a really messy and confusing space right now! It used to be rather clear cut - States who legalise cannabis of any kind were in violation of federal law, and that included CBD. But then the Farm Bill passed in 2018, which had the effect of removing cannabis hemp crops from the Controlled Substances Act. And by association, the CBD that can be extracted for those crops. At least, that's what many people argued the Farm Bill did.

In actual fact, it was a bit more complicated than that. And it caused a lot of confusion. The DEA initially came out quite strongly and clearly said that in their opinion, CBD was still illegal. But that didn't really stop anyone, and they have since had to soften their stance as it just isn't practical or politically desirable to prohibit CBD. Now they're playing catch-up trying to put in place some kind of regulations around CBD products, but basically the cat's out of the bag at this point, and widespread semi-regulated CBD is here to stay, in my opinion.

From here, what might happen is the DEA/FDA come out with clear quality, safety, labelling etc. standards for CBD products and essentially permit them as food, and crack down only on those who make medical claims (which would include describing the psychological effects of CBD) or who fail to meet their standards. But at the same time, CBD will be keep being sold in dispensaries and prescribed as a medicine by doctors.

There is a massive supply problem here in Australia, especially for flower (not to mention the cost...) - short of breaking the law or moving to the ACT and growing our own, what do you foresee changing policy and law wise to alleviate this, and when?

Or do the politicians think everything is fine and just don’t care?

Yes, there is a big supply problem right now in Australia. And sadly this is not uncommon. Supply interruptions happen fairly regularly, and it can be a huge problem for patients, especially when it's a widely-prescribed product that lots of people are using.

This can be due to unexpected demand, shipping issues, recalls, or any number of things. Cannabis companies are all relatively new at this and are figuring out production forecasts and supply chains as they go, so these interruptions will keep happening for some time.

Large-scale local cultivation will help, but commercial regulations right now are too restrictive. That is changing slowly, and hopefully in a couple of years time we won't have these issues any more.

In 2017 the NHTSA submitted a report on cannabis impaired driving to Congress ( https://www.nhtsa.gov/sites/nhtsa.dot.gov/files/documents/812440-marijuana-impaired-driving-report-to-congress.pdf ), one interesting observation was that significant impairment had primarily been observed only in simulator studies and only relatively minor driving impairment in actual driving studies. Has there been any further published investigation into why this occurs?

Yes there has and I have seen this in my own research too. Cannabis impairment does appear to be exaggerated in the simulator, in that the observed magnitude of impairment is greater during simulator driving when compared with on-road driving. If you have a look at our recent on-road driving study here - https://jamanetwork.com/journals/jama/article-abstract/2773562- you will see that THC produced relatively minor driving impairment, similar to the effects of low dose alcohol, while an equivalent dose in the simulator produced what looked like a greater level of impairment - https://pubmed.ncbi.nlm.nih.gov/31044290/

What are you all opinions on the safety of cartridges, specifically delta-8 cartridges that have recently become popular?

If cannabis vape cartridges are manufactured properly, they should be no more physically harmful to use than a nicotine vape. The effects of vaporised inhaled delta-8 have not been properly studied to the best of my knowledge.

However, many vape carts - especially unregulated, illicit ones - have not been manufactured properly. This is what led to the 2019 'popcorn lung' scare in the US. Many people were harmed and some sadly died. It was believed that vitamin E acetate, used as an ingredient in the vapes, led to this. But that could happen in a cannabis vape or a nicotine vape.

Can you recommend any studies to read that contain good data on blood THC concentration after certain durations? example after eating 20mg THC gummy how long until 5 ng per ml is detectable?

This paper by Ryan Vandrey and colleagues might be what you are looking for?

https://www.sciencedirect.com/science/article/abs/pii/S0376871620301344