Author

Claude A. Curran MD

Browsing

Neuropsychopharmacology

. 2022 Jan 8. doi: 10.1038/s41386-021-01259-0. Online ahead of print.

Identification of ∆9-tetrahydrocannabinol (THC) impairment using functional brain imaging

Jodi M Gilman 1 2 3William A Schmitt 4 5Kevin Potter 4 6Brian KendziorGladys N Pachas 4 6Sarah Hickey 4Meena Makary 5 7Marilyn A Huestis 8A Eden Evins 4 6Affiliations expand

Abstract

The primary cannabinoid in cannabis, Δ9-tetrahydrocannabinol (THC), causes intoxication and impaired function, with implications for traffic, workplace, and other situational safety risks. There are currently no evidence-based methods to detect cannabis-impaired driving, and current field sobriety tests with gold-standard, drug recognition evaluations are resource-intensive and may be prone to bias. This study evaluated the capability of a simple, portable imaging method to accurately detect individuals with THC impairment. In this double-blind, randomized, cross-over study, 169 cannabis users, aged 18-55 years, underwent functional near-infrared spectroscopy (fNIRS) before and after receiving oral THC and placebo, at study visits one week apart. Impairment was defined by convergent classification by consensus clinical ratings and an algorithm based on post-dose tachycardia and self-rated “high.” Our primary outcome, PFC oxygenated hemoglobin concentration (HbO), was increased after THC only in participants operationalized as impaired, independent of THC dose. ML models using fNIRS time course features and connectivity matrices identified impairment with 76.4% accuracy, 69.8% positive predictive value (PPV), and 10% false-positive rate using convergent classification as ground truth, which exceeded Drug Recognition Evaluator-conducted expanded field sobriety examination (67.8% accuracy, 35.4% PPV, and 35.4% false-positive rate). These findings demonstrate that PFC response activation patterns and connectivity produce a neural signature of impairment, and that PFC signal, measured with fNIRS, can be used as a sole input to ML models to objectively determine impairment from THC intoxication at the individual level. Future work is warranted to determine the specificity of this classifier to acute THC impairment.ClinicalTrials.gov Identifier: NCT03655717.

Previous generations observed a clear association between marijuana use, mental illness, and addiction.  With opiate overdoses are ever increasing what justifies encouraging the use of this gateway drug?  Is it all about tax revenue?  If cannabis actually triples the rate of Schizophrenia and psychotic illness the costs for medical treatment will be many times the tax revenue generated by cannabis sales!  

CANNABIS, TOBACCO,  AND OTHER DRUGS

Cannabis use can increase the likelihood of using other substances including tobacco.  

Over 500 compounds have been identified in Cannabis Sativa (the most marketed strain of Cannabis species).  Little is known about the individual properties of each component.  Some may be beneficial but others may cause harm.  Who knows?

Singapore launched a project to develop medicinal cannabinoids in an effort to identify the beneficial chemical components of cannabis in order to provide safer, more accurately targeted therapy.

Constituents of Marijuana  

Cannabinoids

CBG (Cannabigerol) type — 17 analogs known, incuding

Cannabigerolic acid A [(E)-CBGA-C5 A]

Cannabigerolic acid A monomethyl ether [(E)-CBGAM-C5 A]

Cannabigerol [(E)-CBG-C5]

Cannabigerol monomethyl ether [(E)-CBGM-C5]

Cannabigerovarinic acid A [(E)-CBGVA-C3 A]

Cannabigerovarin [(E)-CBGV-C3]

Cannabinerolic acid A [(Z)-CBGA-C5 A]

CBC (Cannabichromene) type — 5 analogs known

(±)-Cannabichromenic acid [CBCA-C5 A]

(±)-Cannabichromene [CBC-C5]

(±)-Cannabichromevarinic acid [CBCVA-C3 A]

(±)-Cannabivarichromene [CBCV-C3/CBCV-i C3]

(+)-Cannabichromevarin [CBCV-C3]

2-Methyl-2-(4-methyl-2-pentenyl)-7-propyl-2H-1-benzopyran-5-ol

CBD (Cannabidiol) type – 9 analogs known

Cannabidiolic acid (CBDA-C5)

(-)-Cannabidiol (CBD-C5)

Cannabidiol monomethyl ether (CBDM-C5)

Cannabidiol-C4 (CBD-C4)

Cannabidivarinic acid (CBDVA-C3)

(-)-Cannabidivarin (CBDV-C3)

Cannabidiorcol (CBD-C1)

Cannabidibutol (CBDB)

Cannabidiphorol (CBDP) 

9– THC type – 11 analogs known

Tetrahydrocannabinolic acid A (9 -THCA-C5 A)

Tetrahydrocannabinolic acid B (9 -THCA-C5 B)

Tetrahydrocannabinol (9 -THC-C5) – available as Marinol (Dronabinol)

Tetrahydrocannabinolic acid-C4 (9 -THCA-C4 A and/or B)

Tetrahydrocannabinol-C4 (9 -THC-C4)

Tetrahydrocannabivarinic acid A (9 -THCVA-C3 A)

Tetrahydrocannabivarin (D9 -THCV-C3)

Tetrahydrocannabiorcolic acid (9 -THCOA-C1 A and/or B)

Tetrahydrocannabiorcol (9 -THCO-C1)

Tetrahydrocannabutol (Δ9-THCB)

Tetrahydrocannabiphorol (Δ9-THCP)

8– THC type – 2 analogs known

()-8trans-(6aR,10aR)-Tetrahydrocannabinolic acid A (8 -THCA-C5 A)

  ()-8 -trans-(6aR,10aR)-Tetrahydrocannabinol (8 -THC-C5)

CBL (Cannabicyclol) type – 3 analogs known

(±)-(1aS,3aR,8bR,8cR)-Cannabicyclolic acid (CBLA-C5 A)

(±)-(1aS,3aR,8bR,8cR)-Cannabicyclol (CBL-C5)

(±)-(1aS,3aR,8bR,8cR)-Cannabicyclovarin (CBLV-C3)

CBE (Cannabielsoin) type – 5 analogs known

(5aS,6S,9R,9aR)-Cannabielsoic acid A (CBEA-C5 A)

(5aS,6S,9R,9aR)-Cannabielsoic acid B (CBEA-C5 B)

(5aS,6S,9R,9aR)-C3-Cannabielsoic acid B (CBEA-C3 B)

(5aS,6S,9R,9aR)-Cannabielsoin (CBE-C5)

(5aS,6S,9R,9aR)-C3-Cannabielsoin (CBE-C3)

CBN (Cannabinol) type – 7 analogs known

Cannabinolic acid A (CBNA-C5 A)

Cannabinol (CBN-C5)

Cannabinol methyl ether (CBNM-C5)

Cannabinol-C4 (CBN-C4)

Cannabivarin (CBN-C3)

Cannabinol-C2 (CBN-C2)

Cannabiorcol-C1 (CBN-C1)

CBND (Cannabinodiol) type – 2 analogs known

Cannabinodiol (CBND-C5)

Cannabinodivarin (CBVD-C3)

CBT (Cannabitriol) type – 9 analogs known

()-trans-Cannabitriol [()-trans-CBT-C5]

(+)-trans-Cannabitriol [(+)-trans-CBT-C5]

(±)-cis-Cannabitriol [(±)-cis-CBT-C5

(±)-trans-Cannabitriol-C3 [(±)-trans-CBT-C3]

CBT-C3-homologue (unknown stereochemistry)

()-trans-10-Ethoxy-9-hydroxy-6a(10a)- tetrahydrocannabinol [()-trans-CBT-OEt-C5]

trans-10-Ethoxy-9-hydroxy-6a(10a)- tetrahydrocannabivarin-C3 [trans-CBT-OEt-C3]

8,9-Dihydroxy-6a(10a)-tetrahydrocannabinol [8,9-Di-OH-CBT-C5]

Cannabidiolic acid tetrahydrocannabitriol ester (CBDA-C5 9-OH-CBT-C5 ester)

Miscellaneous Cannabinoids – 14 analogs

Dehydrocannabifuran (DCBF-C5)

Cannabifuran (CBF-C5)

 Cannabichromanone (CBCN-C5)

Cannabichromanone-C3 (CBCN-C3)

Cannabicoumaronone-C5 (CBCON-C5)

Cannabicitran (CBT-C5)

10-Oxo-6a(10a)-Tetrahydrocannabinol (OTHC)

()-9 -(6aS,10aR-cis)-Tetrahydrocannabinol 

    [()-cis9 -THC-C5]

Cannabiglendol-C3 (OH-iso-HHCV-C3)

()-(6aR,9S,10S,10aR)-9,10-Dihydroxyhexa-

    hydrocannabinol [()-Cannabiripsol-C5]

()-6a,7,10a-Trihydroxy-9 -tetrahydrocannabinol 

    [()-Cannabitetrol]

(±)-7 -cis-(1R,3R,6S)-Isotetrahydrocannabivarin-C3

()-7 -trans-(1R,3R,6R)-Isotetrahydrocannabivarin-C3

()-7 -trans-(1R,3R, 6R)-Isotetrahydrocannabinol-C5

Non-Cannabinoids

Nitrogenous Compounds –27

Amino Acids – 18

Proteins, enzymes, and glycoproteins – 11

Sugars and related compounds – 34

Hydrocarbons – 50

Simple Alcohols – 7

Simple Aldehydes – 12

Simple Ketones – 13

Simple Acids – 20

Fatty Acids – 23

Simple esters and lactones – 13

Steroids – 11

Terpenes – 120

Non-cannabinoid phenols — 25

Flavonoids – 23

Vitamins – 1

Pigments – 2

Elements – 9

OVER 500 CONSTITUENTS

Mahmoud A. ElSohly a,b , Desmond Slade a 

a National Center for Natural Products Research, School of Pharmacy, 

The University of Mississippi, University, MS 38677, USA 

b Department of Pharmaceutics, School of Pharmacy, 

The University of Mississippi, University, MS 38677, USA

A Novel Phytocannabinoid Isolated from Cannabis Sativa L. with an In

Vivo Cannabimimetic Activity Higher Than Δ9-tetrahydrocannabinol:

Δ9-Tetrahydrocannabiphorol

CinziaCitti, Pasquale Linciano, Fabiana Russo, Livio Luongo, Monica Iannotta,

Sabatino Maione, Aldo Laganà, Anna LauraCapriotti, Flavio Forni, MariaAngelaVandelli,  GiuseppeGigli, GiuseppeCannazza

There is not much discussion about “Cannabis-Induced Psychosis” despite the clinical evidence of its existence.  Health insurers  and Health Maintenance Organizations undoubtedly have amassed data about the incidence of and expenditures for cannabis-related psychiatric and medical disorders (see cannabis-induced hyperemesis,  myocarditis, pericarditis, obesity, respiratory disorders).  

Marijuana use is associated with an increased risk for the development of psychosis and psychotic disorders such as schizophrenia.   Although this risk was recognized long ago there’s an ongoing chicken-and-egg debate exculpating cannabis per se by suggesting that subclinical schizophrenics are more inclined to use it hence unmasking their pre-existing psychotic tendency.   Cannabis doesn’t cause psychosis, people do!

So where have the health insurance companies been?  How much do they spend annually for the treatment of cannabis-induced psychotic illnesses?  What are their projected yearly expenditures?  Have they observed an increase in psychiatric admissions in persons who test positive for cannabis?  How about in cannabis users simultaneously taking Adderall or other psychostimulants?   Are they simply investing in more rehabs, detox facilities, and drug companies making anti-psychotic medications?  Does cannabis use increase or decrease their profit margins?  

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Marinol (Dronabinol) is a synthetic formulation of the THC isomer Tetrahydrocannabinol (∆9 -THC-C5). It is a generic medicine and has been available for many years. Dronabinol is used to treat loss of appetite, nausea, and vomiting associated with AIDS and cancer.  Like cannabis Dronabinol also carries a risk of developing psychosis but being a pill it is easier to control the dose; the smallest dose is 2.5mg. 

With  Dronabinol grandma will not be exposed to the 500+ mysterious chemicals in weed or to the 110 known toxins included among the 2,575 chemicals in marijuana smoke.

It is a safer alternative! And as a generic medication Dronabinol has a more compassionate price than cannabis!  

Cesamet (Nabilone) is similar to Marinol (Dronabinol).