# 20190630 Sun DOY=239 DOW=Sun [[q-Aug27]] | [[q-20190628|prior]] <> [[q-20190701|next]] --- # [[ICRS2019]] Sun 20190630 Bethesda **International Cannabinoid Research Society** #ICRS **Day1** | [[q-20190701|Day2]] | [[q-20190702|Day3]] | [[q-20190703|Day4]] #GR19 notebook page: [[20190630 q-GR19 pg03|03]] [[20190630 q-GR19 pg04|04]] [[20190630 q-GR19 pg05|05]] [[20190630 q-GR19 pg06|06]] [[20190630 q-GR19 pg07|07]] [[20190630 q-GR19 pg09|09]] [[20190630 q-GR19 pg10|10]] [[20190630 q-GR19 pg11|11]] .0730 Breakfast .0830 Welcome & Opening Remarks ## .0845 Oral Session 1. Cannabis Compounds, Genetics, Chemovars and Extraction Methods * Chairs: Jana Hajslova and John McPartland ### 1. Renaming Dinosaurs: Exhuming the Ancestors of “Sativa” and “Indica” * [[John McPartland]], Guy * RESULTS: Evidence traces “`Sativa`” to South Asia (India). It spread to the Middle East, Africa, and Southeast Asia by the 1200s. Europeans in India began assigning names in the 1500s, and preserving herbarium specimens in the 1600s. “Sativa” spread to America during the African slave trade, and spread to European medicine after O’Shaughnessy. They all share South Asian heritage. Europeans in Central Asia first described “`Indica`” (using other names) in the 1600s. By the 1800s British botanists collected Central Asian specimens from Afghanistan and Turkestan, and analyzed their phytochemistry. Afghani germplasm was smuggled into the USA in 1971, and cross-bred with “Sativa”. Within 15 years, unhybridized plants of South Asian and Central Asian heritage had become difficult to obtain. Research on South Asian and Central Asian plants collected in the 1970s–1990s showed phytochemical and genetic differences. These differences began to disappear in 21st century studies of hybridized “Sativa” and “Indica”. * DISCUSSION: The nomenclaturally legitimate variety names for the ancestors of “Sativa” and “Indica” are var. `indica` and var. `afghanica`, respectively. They are domesticated forms. Their wild-type progenitors are named var. `himalayensis` and var. `asperrima`, respectively. Widespread crossbreeding between indica and afghanica has obscured taxonomic differences. ### .0845 2. Short- and Long-term Acute Effects of Cannabis on Headache and Migraine: a Naturalistic Study of Medical Cannabis Users > [[20190630 q-GR19 pg03|pg03 notes]] * Carrie Cuttler; Spradlin; Craft * 20k cannabis sessions via StrainPrint > 50% decr in migraine severity * M>F in sx reduction * used COA data, not input from pts * Limitations: self-selected pop - no placebo - self-described “HA” and “Migraine”. * Q&A: * John Tamlin, Cannabis Insights, asked a Q. * `StrainPrint` doesn’t have much info re terpenes or minor CBs. ### .0900 3. Chiral Endocannabinoid Ligands > [[20190630 q-GR19 pg03|pg03 notes]] * Spyros P Nikas, Northeastern Univ CDD Ctr for Drug Discovery * AEA analogs - `AMG315` = dimethylanandamide * chiral enantiomers can be quite dif in Ki (3 magnitudes), with the S > R. * To achieve these objectives, we analyzed global data from the app `StrainPrint`. This app provides patients with a means of tracking changes in symptoms of a variety of medical conditions as a function of different doses and strains of cannabis. Specifically, patients indicate the symptom they are experiencing, rate its severity on a 0-10 scale, enter the strain they are about to use (THC and CBD content are obtained from Canadian licensed producers), enter the method of ingestion and dose (number of puffs) of cannabis used, and then re-rate their symptom severity 20 mins to 4 hrs after cannabis use. The sample used in the present study contained 1,587 individuals who used the app over 15,000 times to track changes in headache severity and 826 individuals who used the app over 10,000 times to track changes in migraine severity. * The results of a series of analyses using multilevel modeling revealed that patients reported a 48.5% reduction in headache severity and a 53.7% reduction in migraine severity following inhalation of cannabis. Men and women reported comparable reductions in headache severity but men reported significantly greater reductions in migraine severity following cannabis use than did women. No main effects or interactions between THC and CBD were detected, and all reported quantities used (1 to 10+ puffs) produced significant reductions in headache and migraine severity ratings. No change in baseline symptoms was detected across time/cannabis treatment sessions, and no tolerance was detected. Instead, larger reductions in migraine severity were reported across time/cannabis treatment sessions. The results indicate that inhaled cannabis reduces self-reported headache and migraine severity by approximately 50%, and repeated use of cannabis to treat headache and migraine does not appear to be associated with tolerance to its effects nor to medication overuse rebound effects. ### .0915 4. Acute Self-administration of Legal Market Flower and Concentrated Cannabis: Cannabinoid Blood Levels, Subjective Intoxication, and Neurobehavioral Outcomes > [[20190630 q-GR19 pg04|pg04 notes]] * L. Cinnamon Bidwell, UColorado Boulder * CO 2017 annual sales data: flower: $815M - concentrate: $353M - edible: $202M * little data on high potency concentrates * using a mobile lab to assess pts using legal market products * ACED = Acute Cognitive Effects of Dabbing * partnered w dispensary, pt randomly assigned to A or B concentrate, we they buy as usual at a dispensary. * 5 days of ad lib use at home, then goes to lab within 60 mins of use (lab parks outside their house). * > not much dif in cog fx btw 70% & 90% THC potency * concentrate [serum] is ~3x that of flower, but they note the same level of high * suggests that concentrate users become tolerant to level * flower users made more errors on delayed memory test * [serum] were highly variable * did balance tests using gyroscope in iPhone * notes sig incr in total movement * impaired balance p conc use that recovered p 1hr * subjects were NOT blinded to potency but investigators were * The concentrate users had higher levels of THC and THC metabolites across all assessments, as well as a stronger peak acute effect for THC. Both flower and concentrate users reported increased subjective drug effects immediately after use; however, levels of subjective intoxication did not differ across flower and concentrate users or by potency within flower or concentrates. Thus, the results indicated that THC blood levels were higher for concentrate users overall and acutely, but that potency did not affect blood levels for either form of cannabis. In addition, despite these differences in blood levels, subjective levels of intoxication did not differ across flower and concentrate groups. Broadly, cognitive effects were minimal even for high potency forms of cannabis. * Conclusions: Findings suggest that users of high potency flower and concentrated cannabis products may demonstrate tolerance to both the subjective and cognitive effects of even very high potency cannabis. In addition, flower and concentrate users may titrate their use to subjective levels of intoxication regardless of product potency. Portably-performed quantitative measures of impaired postural stability appear to be responsive to acute use even in regular users. ### .0949 5. Assessing Trends of CBD Oils Quality at the EU Market > [[20190630 q-GR19 pg05|pg05 notes]] * Jana Hajslova; Benes; Russo (Prague) * Used ISO17025 methods * []lu EMCDDA (EU NIDA, essentially) * we decided to assess the quality of CBD oils available at the EU retail market focusing not only on CBD, but involving also Δ9-THC and PAHs as quality indicators. In total, 70 CBD oil samples were collected within three sampling campaigns performed within the years 2016-2019. * CBD: 65% compliant (2016); 85% (2017-18); 75% 2019 * THC: present in ALL samples (2016); in 80% of samples (2017-18); in 92% of samples (2019). Most were not labeled as such. * EFSA = Eur Food Safety Auth (FDA equiv) * 39% of samples had greater than the allowable limit of BaP benzo-a-pyrene (<2ug/kg) * sum of 4 PAHs = 57% were higher than limit of 10ug/kg * The results of chemical analyses showed significant issues in all of the monitored quality indicators. The lower than declared amount of CBD or its missing content information was observed in over 20% of the tested samples. ... The results of Δ9-THC content were even worse. Although we detected this psychotropic compound in 89% of the oils, in most cases, no information on Δ9-THC presence was provided at the label. Considering the consumer with a body weight 70 kg, the ARfD was exceeded by almost 50% of samples with the highest Δ9-THC dose being even 4800% of the ARfD. Such observation is alarming as even relatively low amounts of Δ9-THC can influence normal function of cognition and impair comsumer’s capacity to drive and make decisions in general. Raising significant personal as well professional life risks for consumer especially when not being aware of the controlled psychoactive substance intake at all. The continuously unsatisfactory situation was observed also in case of PAHs (polyaromatic hydrocarbons), which were detected in all of the tested CBD oils. The legislative limits for BaP and/or Σ4 PAHs were exceeded in 60% of the samples with maximum concentrations being even 9- and 19-fold higher than maximum limits, respectively. >[!summary] Conclusions: > * need declaration on label for THC > * [CBD] is usu compliant > * high contamination with PAHs > * pesticide residues are usually polar and generally do not get into the oils > * there is a move to designate CBD as a “novel food”. ## .1030 Oral Session 2. Cannabidiol * Chairs: Michelle Glass and Saoirse O’sullivan ### 6. Acute and Chronic Effects of Cannabidiol on Haemodynamics in Healthy Males >[[20190630 q-GR19 pg06|pg06 notes]] & [[20190630 q-GR19 pg09|pg09 notes]] * Saoirse E O’Sullivan; Sultan ### 7. High Anxiety? Examining the Impact of Four Weeks of Treatment With a Novel High Cannabidiol Product >[[20190630 q-GR19 pg10|pg10 notes]] * Staci A Gruber ### 8. Acute Pharmacokinetics and Pharmacodynamics of Oral and Vaporized Cannabidiol in Healthy Adults >[[20190630 q-GR19 pg11|pg11 notes]] * Tory Spindle; Bigelow; Flegel; Vandrey ### 9. Cannabidiol Attenuates Cocaine Reward By CB2, 5-HT1a and TRPV1 Receptor Mechanisms in Rats * Ewa Galaj ## .1130 US Cannabis Policy: Implications for Public Health * Susan Weiss, Ph.D. - Director, Division of Extramural Research, NIH * PLENARY SPEAKER .1230-1330 Lunch ## .1330 Cannabinoid Pharmacology: My First Half Century (Pertwee) * [[Roger Pertwee]], M.A., D.Phil, D.Sc., HonFBPhS - Emeritus Professor, Institute of Medical Sciences, University of Aberdeen, Scotland * **Lifetime Achievement Award** - started in Oxford, with Tincture of Cannabis. - Cannabinol was first CB to be isolated and synthesized - Nature1970.Gill. First paper? - mouse tetrad of tests on locomotor, pain, catalepsy, and hypothermia - 1977 found effect of CB on hypothalamus that regulates mouse body temperature (downwards) - MolecPharm 35: discovery of receptor - CB1 & CB2 receptors 44% homologous - 1992 Mechoulam discovered anandamide - BrJPharm1993.Pertwee paper on cross-tolerance of THC, anandamide, and WIN ag - (R)-methananandamide - AM281, ACEA - ICRS formed after idea came at Crete mtg in 1990 - first mtg in CO in 1992, “never the Cannibal Society” - **The re-medicalization of cannabis** - [[Clare Hodges]] - Br Med Assoc wrote paper re Clinical Cannabis Group - House of Lords in 1998 voted to explore medical cannabis further - Explained how he started with anecdotal pt evidence and worked towards scientific evidence - GW Pharm > _Sativex_ - In UK, medicinal cannabis moved to Schedule 2 - **Synthetics** - O-1057 water soluble form of THC - THC-Val-HS - water soluble THC pro-drug - AAPS Journal2005.Pertwee vol7. - “autoprotective” function of eCB system - Mrs Jo Cameron has no anandamide breakdown enzyme, she feels no pain (FAAHase) - ProcNutritionSociety2014.Pertwee 73:96 eCB, increasing levels - allosteric modulation by increasing binding or increasing signaling - ACSChemNeurosci2017.LaPrairie CB1 allosteric mod. - CBD may be a negative allosteric modulator of CB1 and CB2 R - BrJPsychopharm LaPrairie - Pepcan-12 as CB2 positive allosteric modulator - CB2 ag reducing viability of CLL cells that express receptors - Fightocannabinoids! - CBD effect on 5HT1AR - BJP 2012, 2013 CBD N/V - CBDA methylester HU-580 - Cascio 2010 - CBDA, HU-580 has bell-shaped response curve, not sigma - Zuardi 1993 ipsapirone and CBD sim for anx - BrazilJPsych2019 - CBD and inverted U response curve - **CBG** - a2R ag —> pain relief - Comelli 2012 - **THCV** - acts as antag at CB1 at low doses, and ag at high doses - may be good for renal nephropathy - d8-THCV may be good for nicotine dependence ## .1430 Oral Session 3. CB1 Pharmacology * Chairs: Resat Cinar and Yossi Tam ### 10. Allosteric Modulators of the CB1-R: Diaryl Ureas * Yanan Zhang, RTI - `Rimonabant`, CB1 antag but depr, anx, SI - Orthosteric modulators bind to TM portion, such as eCBs - MedChemRev2017.Nguyen CB1 allosteric mods, eg PSNCBAM-1 a PAM ag? ### 11. Structural Analysis of the CB1 Cannabinoid Receptor Interacting Protein 1a (CRIP1a) * Allyn C Howlett - `CRIP1a` - CB Receptor interacting Protein - AA sequence of CRIP1a has no known homology with any other known protein - worked out crystal structure - 10-stranded beta-barrel with one gap btw 2 strands - is sim to transport protein, PDE6delta - Does CRIP sequester G-proteins? ### 12. Cannabinoid-1 (CB1) Receptor Regulates Soluble Leptin Receptor Levels via C/EBP Homologous Protein (CHOP), Contributing to Obesity-related Hepatic Leptin Resistance * Adi Drori - adipocyte-secreted leptin signals brain re energy homeostasis. - `LEPR` = Leptin receptor - `SLR` = Soluble Leptin Receptor, main leptin-binding protein in plasma - SLR may be involved in regn of obesity - eCB system modulates leptin resistance - CB1R blockade restores SLR levels - hepatic CB1R impacts SLR levels > obesity - Endoplasmic reticulum (ER) stress, via accum of proteins in the ER - impacts obesity - CHOP levels are correlated with SLR - CHOP KO reverses CB1R-induced SLR down-regulation ### 13. MRI-1867 - A Third Generation CB1-R Antagonist, for Effective Therapy of a Rare Disease, Hermansky-Pudlak Syndrome Pulmonary Fibrosis * Resat Cinar - HPS is rare autosomal recessive disorder w 10 human subtypes, predominant in north part of Puerto Rican heritage - oculocutaneous albinism, bleeding diathesis, granulomatous colitis, pulmonary fibrosis - no tx - in the lung disease, 3 cell types involved, so complex pathology - `S-MRI-1867` is lead compound - increased anandamide levels negatively correlated with pulm fibrosis in HPS pts - pale ear mice are HPS model ### 14. A Critical Evaluation of Terpenoid Signaling at Cannabinoid CB1 Receptors in a Neuronal Model * Alex Straiker - mangoes have Myrcene and some think eating mango improves high from MJ - looked at myrcene, linalool, pinene, linalool, nerolidol - used 1uM concentrations in neurotransmission model - Myrcene - not much effect - Linalool - no effect - Limonene - some impact c/w CB1 antag - a-Pinene - mild inhibit of CB signalling - Nerolidol - solid CB1 inhibition evidence - 2-AG results suggest a postsynaptic mechanism - 1gm Myrcene = 5000 mangoes! - [] cannador.com ### 15. Hybrid Inhibitor of Peripheral CB1 Receptor and Inducible Nitric Oxide Synthase Mitigates the Development of Dyslipidemia * Tony Jourdan, INSERM ## .1600-1800 Poster Session 1 * P1-1 * P1-3 ! Cannabinoidomics – an Analytical Tool to Understand the Effect of Medical Cannabis Treatment * P1-6 ! Lack of Standardization in Cannabis Variety Names in Both Grey Market and Legal Supply Chains in Canada: Evidence for Necessity of Genetic Verification * P1-12 * P1-13 * P1-15 ! Compounding of Cannabis Products with Specific Plant Derived Essential Oil Constituents for Targeted Therapies * P1-16 * P1-18 * P1-19 ! Variability and Paucity of Medically Relevant Cannabis Products in State Regulated Cannabis Retail Dispensaries * P1-29 * P1-30 ! Chemical Composition--Activity Analyses of 59 Medical Cannabis Samples -- a Medicinal Chemistry Approach * P1-31 * P1-34 * P1-36 * P1-38 ! Potency of Cannabis and Related Products in the USA During the Period 2008-2018 * P1-40 * P1-43 * P1-44 * P1-46 * P1-47 * P1-48 ! Identification of Sex, Strain, and Entourage Effects in the Behavioral and Physiological Response to Cannabinoids * P1-50 * P1-54 * P1-56 a-Terpineol - neuropathic pain * P1-59 ! Applying Machine Learning to Cannabinoid Drug Discovery with Assay Central #ml --- $20190630 90m #QI