Cannabidiol - Science topic

Hi,

NMR is relatively accurate, or you can purchase a standard sample of canabidiol and compare it using methods such as TLC or GC.

Dear Andrew, thank you for your and response and father explanations. Using "dehydrated ethanol, cannabidiol, sodium methoxide, ammonia, HCL and add H₂O₂ and Au if its possible to gold plate it" sounds like a wonderful idea taken directly from the laboratory of an alchemist. Don't forget to apply cell phone radiation to double the reaction rate! 😎😂 However, what looks good on paper does not always work in practice. For example, you will never be able to form lithium hydride (LiH) from lithium chloride and solution. In earnest, it would be helpful if you could tell us what your actual goal is. First of all, it might be useful for you to read the following very instructive review article about the derivative chemistry of cannabidiol:

Fortunately this article has been posted by the authors as public full text on RG. Thus you can freely download it as pdf file. On page 7 of this review article you will find a paragraph on halogenated cannabidiol derivatives. It is stated here that (citation): "The first reported halogenations occurred at the 3′ and/or 5′ positions by chlorine, bromine or iodine substitution, allowing the preparation of 3′-ClCBD, 3′,5′-diCl-CBD, 3′-Br-CBD, 3′,5′-diBr-CBD, 3′-I-CBD, and3′,5′-diI-CBD." I hope this helps.

Good luck with your work and best wishes!

Hi Samiee,

I refer to the product information of cannabidiol from Cayman Chemical.

Solubility of cannabidiol in DMSO is 50 mg/mL which is much sufficient for diluting to DMSO:saline. You could try dissolving cannabidol with DMSO in 30 mg/mL or higher, and then serial dilute to 3 mg/mL (15 mg/kg for 20 g mice and 100 uL injection volume) with saline. Another choice is corn oil which could use for replacing saline as corn oil.

Please also go through the following useful link.

Thank you all.

Please also see the following RG links.

To some extend, what is the exact question?

Old post, thought I'd offer some insight.

Richard Augimeri I'd imagine the sweet spot for winterization is around -40C/F for the solution itself with somewhat diminishing returns from there (something to further consider for scaled commodity production). -80C and agitation certainly speeds up the process as this is a brute force precipitation and we have had similar experience completing the process in 1-2 hours. I would be most focused on the final filtration stage at <1 micron which can be done in-line without a secondary winterization.

Dilution ratios from 3:1 to 10:1 work reliably, depends on the volume of impurities there is to precipitate out. Naturally at 3:1 the mixture is quite viscous and more difficult to filter as well as nearly impossible to filter when impurity volumes are significant. Greater dilution comes at the cost of more time in solvent recovery and handling of greater volumes of volatile solvent, so consider the compromise.

A more non-polar solvent with steep saturation curve per temperature would be far more efficient, but winterization with I-A volatiles is not desirable to everyone.

Also, it has not been my experience that cannabinoids would precipitate out of the solution in a winterization scenario at -80C. This would not be the circumstance for nucleation and the development of isolated solids. Arguably the winterization process, itself, could be described as an 'oiling out.'

Amanda Felske Regarding utilizing a filter reactor for winterization, the cost vs throughput would be difficult to justify outside of a bench research capacity (where it is quite useful for process development). Aside from the volume of the FR vessels themselves, the limited surface area on the filter plate would result in regular blinding which would require draining of the entire vessel from the lid to then replace the blinded filter pad. Bag mechanical filtration to lenticular may be a better choice for production.

For reference, we pre-heat & pre-mix via in-line homogenization and then pre-chill prior to injecting into the chilled holding vessel. The minutes add up when you consider all the actual steps in the process beyond the precipitation itself. Fairly intricate system at scale, whereas a deep freezer and a Buchner is sufficient for cheap, kilo production (though, with a filter reactor being ideal on the bench).

Yep, no need to winterize when done right. :)

I'm easy to reach whether for turn-key systems or a constructive conversation. Good luck out there everyone!

Dear Chloe, I faced with a phenomenon - a drug with a single concentration induced different cellular responses. The error was in a slightly different concentration of the cells themselves. It is always worthwhile to calculate the specific concentration, mol / cell. successful experiments!

Yes! Please take a look at these useful RG links.

Store it in DMSO in the freezer. Use multiple centrifuge vials so you can take one sample at the time of analysis.

Please take a look at this RG useful link.

It would be very interesting to know how each of the various oils in CBD including minute traces of THC, as Marc Mathys and you both mentioned, are contributors to its therapeutic effects.

I would suggest a paper we did in Nature 1993 in which we showed, beyond any reasonable doubt, that it was used for specific medical purposes in the 4th cent. CE for women having difficulty with childbirth. I believe that its impt in that heretofore, we knew it was used for medical purposes from the literature but no physical evidence had been as of yet discovered. As it increases the frequency and power of the contractions and is easily available today, it could easily be incorporated into the pharmacology of developing nations. They just have to be made aware.

As the molecular mechanisms are the same in in vulvodynia and fibromyalgia, and the two often are co-morbid, this might be an answer:

The best extraction method depends on the finished product you want to obtain. As a general lab test to get good quality and purity I suggest to go for QWET extraction by using lab/food grade 200 proof ethanol (NOT Denatured). The starting material should be dry (humidity<10%) and fine-milled (1mm). The ethanol shall be cold as well in order to minimize the presence of polar compounds such as chlorophyll in the extract. At a temperature around -30°C you should be able to maximise the cannabinoids (non-polar) and cannabinoid-acids (polar) yield while minimizing the undesirable compounds (chlorophyll, waxes ...) that will be kept frozen in the plant material. Dry-ice crumbs in ethanol will help obtaining a quite effective slurry, while a vacuum chamber and/or gentle stirring will accelerate the process reducing the extraction time to approx. 15-20min. so prepare the cold ethanol with a lab freezer or simply mix some dry-ice and ethanol in a separate container: ethanol shall be at least in a 4:1 ratio with the green matter. In a stainless steel container mix the milled plant material with dry-ice crumbs, stir and let it rest for 10 min, then add cold ethanol and gently stir during 15-20min (don't wait until dry-ice is completely dissolved or undesirables will defreeze and be extracted). The resulting tincture shall be then well filtered (25µm mesh or smaller) to avoid plant particles. If you need a very clear oil, let the tincture rest in freezer (-18°C) for 12 hours and remove the lipids collecting on the surface (winterization). As last step evaporate the ethanol at low temperature to minimize the loss of highly-volatile terpenoids (at 20°C) or at moderate temperature (40+°C) if you don't mind losing some of them.

Hi Dr. Ihnat,

Recently, a cross-sectional study of CBD use patterns in the US found that a majority (62%) of CBD consumers have reported using it to treat medical conditions (Corroon & Phillips, 2018). Importantly, pain was by far the most common medical condition for which CBD was used. Among those using CBD to treat pain, the majority reported believing that CBD works “very well” to “moderately well” for relieving their pain. Despite its frequent use as an analgesic treatment, no published experimental research has ever tested the analgesic effects of pure CBD on pain in humans (that I'm aware of anyway). There have been some animal studies that have shown promise for CBD, but its too early to tell how well this translates into research with humans. There are some ongoing trials that will hopefully shed some light on the topic. For the time being, there isn't strong evidence either which way.

DOI for the reference: 10.1089/can.2018.0006

Perhaps THC Pharm, Bionorica, or STI Pharmaceuticals know people who can help you. Good luck.

As a BHC clinician of over 40 years, my professional observations follow. The native plant from which MJ originates is very rich in compounds, of which THC is the best known psychoactive compound. It readily binds w/ lipids and very easily crosses the BBB! We need a lot more research on the other compounds. As a clinician, I am very cautious about clinical applications. I treat some folks w/ SUD. They all tend to be poly sub abusers.

Here in the US, I tentatively support CBL's for clinical purposes. On clinical grounds, I do not recommend recreational usage. The vast majority of my clients are already seriously compromised.

Thanks much for offering this topic. I could go on and on in this regard.

Rich

MAPK and cytokines in general are considered key factors in chronic pain, whereas they are linked to expressed microglia in chronic pain conditions.

Hi, I have used the following preparation for other CB1r ligands and it has worked very well. I have not specifically tried it with CBD however.

Dissolve 10 mg ligand (CBD) in 50uL DMSO. Bring solution to 37C and vortex repeatedly for 3-5 minutes. Add 5mL of TEG (tetraethyleneglycol). Bring solution to 37C an vortex repeatedly 3-5 mins. Mix this solution 1:1 with saline containing 1% cremaphor (prevents precipitation). Final solution will be at 1mg/mL in 49.5% TEG, 49.5% Saline, .5% DMSO, and .5% Cremaphor.

Thank you S. Béatrice Marianne Ewalds-Kvist :)

I do not know enough about endorphins to respond.

The CBD question is because animal models and Tomida work on THC show CBD may causes transient spiking of IOP. If it does, this a major concern for those taking high doses or topical application for corneal healing.

Straiker has a paper at ARVO this May covering some this in his rabbit model.

Thank you everyone. These sources may help me with my own question. If you specifically know the answer please let me know.

Do you know which fat(s) in the blood stream THC is absorbed into when inhaled? I have not had any luck finding the answer through my usual sources. Thanks

Are any of these fat sources more likely to bring THC into the brain?

May be the following publication can help you: https://academic.oup.com/annonc/article/24/7/1867/190724/Genome-wide-discovery-of-genetic-variants

I would check the FDA to see what they got. Next check chemical databases like chemspider that provide all sorts of info in that regard. maybe check these stats for the proprietary analogs of cannabidiols that have been recently produced...those should have PD/PK profiles.

There are now numerous studies reporting both positive and negative side effects of CBD. for example, Hussain, S. A., Zhou, R., Jacobson, C., Weng, J., Cheng, E., Lay, J., et al. (2015). Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy & Behavior, 47, 138-141.

This is purely anecdotal, but perhaps worth mentioning. Our son has MECP2 Duplication Syndrome. Individuals with this syndrome are typically considered to be on the autism spectrum and most meet the criteria for autism. However, there are many other issues including intractable epilepsy. Our son and some others with the syndrome have been prescribed CBD to control seizures. SOME individuals with the syndrome have made good progress with seizures (for example, 50% reduction in seizure frequency with 50% reduction in anticonvulsants) but what has been more obvious to us and is supported by some research is that our son's alertness and communication improved significantly with the introduction of CBD. Other symptoms of autism (e.g., self-stim behavior) have not changed. I can only speculate, but I believe the improvement in some features in autism is secondary to a reduction in epileptiform brain activity. So, CBD (what he takes is lab tested CBD with 0% THC) might be helpful for those with autism and serious seizure disorders, whether or not it is helpful to autism when seizures are not present. The reference to research on behavioral improvements with CBD so far is not specific to autism, but some seizure studies report changes that could be helpful in autism, for example, Hussain, S. A., Zhou, R., Jacobson, C., Weng, J., Cheng, E., Lay, J., et al. (2015). Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy & Behavior, 47, 138-141.

Dear Tasha,

      I have researched the effects of THC and CBD on night vision, which THC improves, presumably at the retinal level. Please see attached article. I would be happy to follow-up with you on additional corroboratory studies.

Cheers,

Ethan Russo, MD

I agree, but the general consensus is that long term use has detrimental effects on cognition and memory. We have to be careful that this doesn't become adderall/Ritalin part 2, where pts can become dependent. For example, with anorexia I am not surprised at the short-term efficacy - my concern is long term dependency and tolerance.  Opioids are great antidepressants and anxiolytics yet most clinicians do not prescribe them for psychiatric patients except in very special cases, eg extreme OCD.  This is all a risk/benefit analysis, but in the case of THC we often don't know the long term effects but we do know that tolerance will develop that will erode efficacy (in some patients, quite quickly)

Before even thinking to look at the possibility of a new drug derived from cannabis, you'll need to demonstrate out of any doubt that Marijuana itself improves vision in LCA patients.  Such a study, if it passes REB, would need to be against a placebo formula (not necessarily easy to formulate but naive subjects, contrary to long standing users,  may probably be fooled by other smokes (french tobacco, for instance), in a randomized, blinded study using standardized, widely used clinical tests investigating visual acuity, contrast and movement perception... etc...   This is the first step.  You have to demonstrate that what YOU are experiencing, can be first documented by scientific methodology and second, that it can be reproduced on others.