THC Potency Research Articles

The contribution of childhood maltreatment to the incidence of heavy cannabis use in Iran (IRNS-CCI): A multicenter, matched-pairs, nested, case-control study

BackgroundPrevious studies have shown the role of the interaction between the endocannabinoid system (ECS) and life's adversities in the formation of addiction, including alcohol abuse. ObjectiveOur objective was to identify childhood maltreatment (CM) patterns with the strongest impact on the probability of heavy cannabis use (THCCOOH concentrations ≥150 ng/mL) in Iran. Participants and settingUsing survivor sampling, 350 adult participants were selected, and they were then allocated to three categories based on an optimal algorithm: 1) Sexual abuse, 2) Physical abuse, and 3) Physical neglect. MethodsFrom 1 September 2019 to 1 May 2023, we implemented a multicenter, matched-pairs, nested, case-control study based on the wave 3-wave 6 data of a longitudinal, multicenter, cohort study. The cases and controls (n = 350 men) were defined according to the severity of CM. The THC potency was evaluated with the delta-9 carboxy tetrahydrocannabinol (THC-COOH) levels in urine using gas chromatography/mass spectrometry (GC/MS). We calculated the population attributable fractions (PAFs) to identify the patterns of maltreatment associated with the highest odds of high-potency cannabis use. ResultsAccumulating CM, including sexual abuse, physical abuse, and physical neglect, carried more than three times the risk of heavy cannabis use (OR 3.4 95 % CI 2.9–4.1), and the combination of the three indicators of maltreatment and a high BMI (25–29.9) carried more than four times the risk of heavy cannabis use (OR 4.7 95 % CI 2.7–4.1) compared to the controls. We estimated that in the case of zero CM for each of the three indicators, over 20 % of new cases of heavy cannabis use can be prevented. ConclusionsThe findings show the significance of CM as a predicator of heavy cannabis use in adulthood and in the abstinence phase.

Quantification of THC levels in different varieties of Cannabis sativa

This literature review paper highlights and updates the THC quantification methods applied for the differentiation of Cannabis varieties and final Cannabis products as a part of the quality control measures. The quantification method also helps to differentiate between Medical Cannabis sativa (drug or marijuana) and Industrial Cannabis sativa L. (Hemp) since THC levels are different. Cannabis has been used for thousands of years for recreational, medicinal, or religious purposes and does not produce Δ9-tetrahydrocannabinol (THC). Tetrahydrocannabinolic acid (THCA) is produced by the cannabis plant as a precursor. The acidic residue of THCA undergo decarboxylation upon heating producing the psychoactive, Cannabinoid, Δ9-tetrahydrocannabinol (THC). A variety of analytical techniques have been developed for quantification and qualification of Cannabinoids and other compounds in Cannabis plant. The most common cannabinoid quantification techniques include color tests, testing gadgets, Cannabinoids direct ELISA Kit, thin layer chromatography (TLC), gas chromatography (GC) and high performance liquid chromatography (HPLC) followed by Fourier transform infrared spectroscopy (FTIR) and Nuclear magnetic resonance spectrometry (NMR). The lack of accurate reporting of THC potency can have impacts on medical patients controlling dosage, recreational consumers expecting an effect aligned with price, and trust in the industry as a whole. Therefore, quantification of final Cannabis product plays an important role in quality control measures. This literature review paper is developed as a part of Cannabis Science awareness programme since Cannabis with 2 different names (marijuana and hemp) is used as a medicine, food and psychotropic drug (THC).

Rational Design, Synthesis, and Characterization of a Solid Δ9-Tetrahydrocannabinol Nanoformulation Suitable for "Microdosing" Applications.

Background: This article highlights the formulation of a solid Δ9-tetrahydrocannabinol (THC)-loaded ingestible prepared from pure THC distillate. Methods: A THC-containing ethanol-assisted cannabinoid nanoemulsion (EACNE) was created using a solvent displacement technique. Subsequently, the EACNE was converted to a solid powdery material while still retaining its THC potency, a format uniquely suited for "microdosing" applications. Results: EACNE had an average lipid droplet size of ∼190 nm, with a polydispersity index of 0.15, and an average droplet ζ potential of -49±10 mV. The nanoemulsion (NE) was colloidally stable for at least 6 weeks, with no meaningful change in cannabinoid potency over the experimental period, as determined by high-performance liquid chromatography analysis. The EACNE remained stable when subjected to physical stresses such as heat, freeze/thaw cycles, carbonation, dilution to beverage concentrations, high sucrose concentrations, and a pH range between 5 and 8. The microencapsulated EACNE demonstrated limited free-flowing behavior but was freely redispersible in water without any visible phase separation. Conclusions: We report the design, creation, and characterization of a THC NE generated without the use of specialized equipment, such as a microfluidizer or a high-pressure homogenizer. This emulsion could readily be converted to a water-redispersible powder. This embodiment is particularly suited for THC "microdosing," a practice that might decouple the health benefits of THC from its psychotropic effects.

Uncomfortably high: Testing reveals inflated THC potency on retail Cannabis labels.

Legal Cannabis products in the United States are required to report THC potency (total THC % by dry weight) on packaging, however concerns have been raised that reported THC potency values are inaccurate. Multiple studies have demonstrated that THC potency is a primary factor in determining pricing for Cannabis flower, so it has an outsized role in the marketplace. Reports of inflated THC potency and "lab shopping" to obtain higher THC potency results have been circulating for some time, but a side-by-side investigation of the reported potency and flower in the package has not previously been conducted. Using HPLC, we analyzed THC potency in 23 samples from 10 dispensaries throughout the Colorado Front Range and compared the results to the THC potency reported on the packaging. Average observed THC potency was 14.98 +/- 2.23%, which is substantially lower than recent reports summarizing dispensary reported THC potency. The average observed THC potency was 23.1% lower than the lowest label reported values and 35.6% lower than the highest label reported values. Overall, ~70% of the samples were more than 15% lower than the THC potency numbers reported on the label, with three samples having only one half of the reported maximum THC potency. Although the exact source of the discrepancies is difficult to determine, a lack of standardized testing protocols, limited regulatory oversight, and financial incentives to market high THC potency likely play a significant role. Given our results it is urgent that steps are taken to increase label accuracy of Cannabis being sold to the public. The lack of accurate reporting of THC potency can have impacts on medical patients controlling dosage, recreational consumers expecting an effect aligned with price, and trust in the industry as a whole. As the legal cannabis market continues to grow, it is essential that the industry moves toward selling products with more accurate labeling.

The Nose Knows: Aroma, but Not THC Mediates the Subjective Effects of Smoked and Vaporized Cannabis Flower

Previous studies have shown that cannabis consumers are willing to pay more money for higher-quality products; however, the definition of “quality” cannabis has not been defined. Despite the known health risks of THC overuse, THC potency has been adopted as the primary market-driving feature of cannabis products. The purpose of this study was to objectively identify features of cannabis that contribute to its appealing subjective effects. In the course of conducting cannabis competitions, commercially available cannabis inflorescences were distributed to healthy volunteers (“judges”) in a randomized, double-blind fashion. Anonymous online survey data about the subjective effects of each cannabis sample were analyzed independently, by researchers not involved with the competitions. Pleasant subjective aroma (but not terpene expression, THC potency, or THC dose) was positively correlated with pleasant subjective effects. There was also a moderate but significant negative association between the amount of cannabis consumed and subjective appeal. These results suggest that, unlike THC potency, pleasant aroma is predictive of pleasant subjective effects. Similar to other agricultural commodities such as coffee and tea, aroma appears to be a robust indicator of the quality of cannabis inflorescence. These findings have wide-reaching public health implications, given the well-established health risks of THC overuse.

Δ9-Tetrahydrocannabinol discrimination: Effects of route of administration in rats

Cannabis users typically smoke or vape cannabis or ingest it in edibles, whereas cannabinoids are typically administered via injection in rodent research. The present study examined the effects of route of administration (ROA) of Δ9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis. Adult female and male Long Evans rats were trained to discriminate intraperitoneal (i.p.) THC from vehicle in a drug discrimination procedure. Following acquisition, dose-effect curves were determined with THC using i.p., oral (p.o.), and subcutaneous (s.c.) injection in both sexes and aerosol exposure in males only, followed by a time course with one dose for each ROA. Both sexes acquired THC discrimination in a similar number of sessions, although baseline response rates were significantly lower in females than males. THC fully substituted for the 3 mg/kg i.p. training dose across all ROA. While potencies were similar for ROA involving first-pass metabolism (i.p. and p.o.), THC potency was lower with s.c. administration. During the time course analysis, aerosol administration had the shortest latency to onset of discriminative stimulus effects and the shortest duration of effect, whereas s.c. administration had the longest duration. The results of this examination of the effects of ROA on an abuse-related effect of THC provide an empirical foundation to facilitate choice of ROA for mechanistic investigation of THC’s pharmacology. Further, animal models using translationally relevant ROA may facilitate more accurate predictions of their effects in humans.

Associations between self-reported cannabis use frequency, potency, and cannabis/health metrics.

Research shows that cannabis use frequency is associated with cannabis dependence and health metrics. However, much less is known about how self-reported cannabis potency (THC and CBD) may be associated with the same metrics, and whether any associations exist after accounting for frequency of cannabis use. Moreover, even less is known about how these relations may differ across cannabis product forms. This exploratory study examined 1) associations between cannabis frequency, potency, and cannabis/health metrics, and 2) whether associations between potency and cannabis/health metrics remained after controlling for frequency of use. Using a sample of adult recreational cannabis users in Colorado (N=300), we tested the relationship between self-reported cannabis use metrics of frequency and potency of flower, edible, and concentrate products with separate measures of problematic cannabis use (i.e., dependence, withdrawal, craving), depression, anxiety, and general perceived health. Greater frequency of flower and concentrate (but not edible) use were associated with greater problematic cannabis use, and greater concentrate use frequency was also associated with more mental health problems. Partial correlations controlling for average frequency of use across all product forms and CBD potency per product showed that one significant association between THC potency and cannabis/health metrics remained (i.e., higher THC concentrate potency with better health), and one emerged (i.e., higher THC concentrate potency with lower cannabis withdrawal). Frequency of use is reliably associated with problematic cannabis use for flower and concentrates, but it did not account for all observed associations in this study. Differences in patterns of associations between frequency and potency and cannabis/health metrics across cannabis forms suggest a need for better understanding user reports of THC and CBD potency, individual differences among users, and improved measurement.

Cannabis potency in North-East Italy: A ten-year study (2010–2019)

This paper presents data about potency of herbal and resin cannabis products seized during 2010–2019 in north-east Italy. More than 12,000 cannabis samples were analyzed and concentrations of THC, CBD and CBN were collected. The results of our study provided clear evidence for an increase in the potency of cannabis products across the study period, which is consistent with other studies. Globally, the median THC concentrations increased from about 6%–11%, but differences were found between herbal and resin materials. THC potency in resin materials increased more consistently across the study period with a dramatic raise during 2018–2019, with median THC contents around 17%.CBD concentrations were found to decrease constantly over the study period, especially in herbal materials, which had a mean CBD concentration of 0.3%. In particular, about 75% of the analyzed herbal samples had a CBD concentration which was less than 3% of the corresponding THC concentration. In contrast, more than 50% of the analyzed resin materials had a CBD concentration which was about 30% of the corresponding THC concentration. This is consistent with the increase in prevalence of high-potency seedless female herbal products observed in the same period and indicates that herbal and resin materials were produced from different varieties of cannabis plants. However, resin materials derived from high THC/low CBD cannabis plants were recently found. Different routes (e.g. northern Europe) or different modalities of distribution were assumed for these products.CBN concentrations were also considered and found to be very low and consistent across the study period indicating reliability of THC values used in statistical analysis.In conclusion, this study provided an accurate picture of cannabis products seized over a decade over a definite geographical area which can be extremely helpful for comparative purposes and for national and international statistical analyses on cannabis products.

Cannabidiol modulation of antinociceptive tolerance to Δ9-tetrahydrocannabinol.

Humans typically self-administer cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) together repeatedly (as in cannabis, cannabis extract, or Sativex®) to relieve pain. It has been suggested that one benefit of the drug combination may be decreased tolerance development. The present study compared the development of tolerance to the antinociceptive effects of THC given alone versus combined with CBD, in rats. THC dose-effect curves on tail withdrawal and paw pressure tests were obtained before and after twice-daily treatment with vehicle or CBD (10mg/kg), plus vehicle or THC (3.6mg/kg females; 9.3mg/kg males) for 4days. On the first day, THC was more potent in females than males on both nociceptive tests. From pre- to post-chronic (day 1 to day 6), THC potency on the tail withdrawal test decreased more in females than males, and rats that had been treated with CBD + THC repeatedly showed greater rightward/downward shifts of the THC dose-effect curve than rats that had been treated with THC alone. Analysis of blood samples taken after day 6 testing showed that serum THC levels were higher in CBD + THC-treated females than in vehicle + THC-treated females, and THC's active metabolite 11-OH-THC and its inactive metabolite THC-COOH were lower in CBD + THC-treated rats than in vehicle + THC-treated rats of both sexes. CBD also increased serum levels of the active metabolite cannabinol in both sexes. The decrease in THC's antinociceptive effects after repeated CBD exposure may be due to CBD-induced inhibition of THC metabolism, and/or antagonism of THC effects that emerges with repeated CBD treatment.

THC potency needs to be tracked.

THC potency needs to be tracked.

The great divide: Separation between in vitro and in vivo effects of PSNCBAM-based CB1 receptor allosteric modulators

While allosteric modulators of the cannabinoid type-1 receptor (CB1) continue to be developed and characterized, the gap between the in vitro and in vivo data is widening, raising questions regarding translatability of their effects and biological relevance. Among the CB1 allosteric modulators, PSNCBAM-1 has received little attention regarding its effects in vivo. Recently, pregnenolone was reported to act as an allosteric modulator of CB1, blocking THC's effects in vitro and in vivo, highlighting the potential of CB1 allosteric modulators for treatment of cannabis intoxication. We investigated the pharmacological effects of PSNCBAM-1 and two structural analogs, RTICBM-15 and -28, as well as pregnenolone, in both signaling and behavioral assays including [35S]GTPγS binding, the cannabinoid tetrad and drug discrimination. While the CB1 allosteric modulator PSNCBAM-1 attenuated THC-induced anti-nociception and its structural analog RTICBM-28 reduced THC's potency in drug discrimination, most cannabinoid effects in mice were unaffected. In contrast to the mouse studies, PSNCBAM-1 and analogs insurmountably antagonized CP55,940- and THC-stimulated [35S]GTPγS binding and exhibited negative binding cooperativity with [3H]SR141716 with similar apparent affinities. Notably, RTICBM-28, which contains a cyano substitution at the 4-chlorophenyl position of PSNCBAM-1, exhibited enhanced binding cooperativity with CP55,940. In contrast to previous findings, pregnenolone did not block THC's effects in drug discrimination or [35S]GTPγS. These data further highlight the difficulty in translating pharmacological effects of CB1 allosteric modulators in vivo but confirm the established pharmacology of PSNCBAM-1 and analogs in molecular assays of CB1 receptor function.

Supplemental Thoughts About Revenue from Marijuana in Vermont

This document is a supplement to a study by the RAND Corporation for Vermont. It represents the views of the author alone, and not of RAND or of the study's other co-authors.It looks at several issues associated with marijuana revenue. First, who might get a break on marijuana taxes? Possibilities include medical card holders, home growers, buyers of favored products, growers that use natural sunlight, and small or large businesses. Second, how much tax can the marijuana market eventually bear? Third, who pays marijuana taxes – (what is the collection point?) – for three possible tax bases, weight, price, and THC potency? Fourth, what other issues might loom?

Non-smoker exposure to secondhand cannabis smoke. I. Urine screening and confirmation results.

Increased cannabis potency has renewed concerns that secondhand exposure to cannabis smoke can produce positive drug tests. A systematic study was conducted of smoke exposure on drug-free participants. Six experienced cannabis users smoked cannabis cigarettes (5.3% THC in Session 1 and 11.3% THC in Sessions 2 and 3) in a sealed chamber. Six non-smokers were seated with smokers in an alternating manner. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Non-smoking participant specimens (collected 0-34 h) were analyzed with four immunoassays at different cutoff concentrations (20, 50, 75 and 100 ng/mL) and by GC-MS (LOQ = 0.75 ng/mL). No presumptive positives occurred for non-smokers at 100 and 75 ng/mL; a single positive occurred at 50 ng/mL; and multiple positives occurred at 20 ng/mL. Maximum THCCOOH concentrations by GC-MS for non-smokers ranged from 1.3 to 57.5 ng/mL. THCCOOH concentrations generally increased with THC potency, but room ventilation substantially reduced exposure levels. These results demonstrate that extreme cannabis smoke exposure can produce positive urine tests at commonly utilized cutoff concentrations. However, positive tests are likely to be rare, limited to the hours immediately post-exposure, and occur only under environmental circumstances where exposure is obvious.

The Ace in the Game: Revenue from Legalized Marijuana

After marijuana is legalized, the costs of producing and selling it will collapse. What will happen to prices? A windfall economic gain will be up for grabs. Policymakers might allow that gain to go to consumers (encouraging consumption) or to cannabusinesses (encouraging production). Or, through revenue measures, they might direct the gain elsewhere (say, to society as a whole). Revenue can be a means, not an end. New revenue for government does not justify legalization of marijuana. New revenue may not cover the costs that legalization creates, and a revenue stream gives government a permanent stake in intoxication. Revenue is only one card in a large deck of drug policy options. But it is the most powerful card.How to play it? The safest, correctable way to distribute an intoxicant is government monopoly, Uruguay style: Retail-only monopoly can match or beat bootleggers’ wares. But monopoly breeds cronyism and corruption, unless power is spread around and transparent. In the United States, states might need to tweak the monopoly model to keep state control over location and price while assigning sales concessions to businesses.A riskier, more awkward plan is for governments to tax commercial distribution, Colorado and Washington style. In the inevitable post-legalization price war, bootleggers will act in a New York minute; Legislatures will not. Taxes are easier for bootleggers to beat than monopoly is. And no tax is perfect. Taxing by THC potency is theoretically appealing, but unworkable. A price tax base has several pitfalls. Even a weight base is problematic.Three other models are possible: auctioning licenses, collective farming, and sales by non-profits. Since no one really knows how to legalize, flexibility to change course is of the utmost importance.

Adolescent Exposure to Chronic Delta-9-Tetrahydrocannabinol Blocks Opiate Dependence in Maternally Deprived Rats

Maternal deprivation in rats specifically leads to a vulnerability to opiate dependence. However, the impact of cannabis exposure during adolescence on this opiate vulnerability has not been investigated. Chronic dronabinol (natural delta-9 tetrahydrocannabinol, THC) exposure during postnatal days 35-49 was made in maternal deprived (D) or non-deprived (animal facility rearing, AFR) rats. The effects of dronabinol exposure were studied after 2 weeks of washout on the rewarding effects of morphine measured in the place preference and oral self-administration tests. The preproenkephalin (PPE) mRNA levels and the relative density and functionality of CB1, and mu-opioid receptors were quantified in the striatum and the mesencephalon. Chronic dronabinol exposure in AFR rats induced an increase in sensitivity to morphine conditioning in the place preference paradigm together with a decrease of PPE mRNA levels in the nucleus accumbens and the caudate-putamen nucleus, without any modification for preference to oral morphine consumption. In contrast, dronabinol treatment on D-rats normalized PPE decrease in the striatum, morphine consumption, and suppressed sensitivity to morphine conditioning. CB1 and mu-opioid receptor density and functionality were not changed in the striatum and mesencephalon of all groups of rats. These results indicate THC potency to act as a homeostatic modifier that would worsen the reward effects of morphine on naive animals, but ameliorate the deficits in maternally D-rats. These findings point to the self-medication use of cannabis in subgroups of individuals subjected to adverse postnatal environment.

The THC content of cannabis in Australia: evidence and implications

ObjectiveTo examine evidence on three claims that: 1) the THC content of Australian cannabis plants has increased up to 30 times; 2) problems experienced by cannabis users have increased in Australia in recent years; and 3) an increase in THC content is the most likely explanation of any increase in cannabis-related problems. MethodsThese claims were assessed by examining data: 1) on THC potency in Australia, the United States and New Zealand; 2) on cannabis-related problems; and 3) from the 1998 National Drug Strategy Household Survey on patterns of cannabis use. Results1) Published data do not show a 30-fold increase in THC potency of cannabis but show a more modest increase in the US. 2) There is suggestive evidence of an increase in cannabis-related problems among people seeking treatment for alcohol and drug problems, juvenile offenders and young adults with psychosis. 3) There are two other more plausible explanations for these reportedly higher rates of cannabis-related problems among adolescents and young adults: (i) more potent forms of cannabis (‘heads’) are more widely used; and (ii) cannabis users are initiating cannabis at an earlier age, thereby increasing the prevalence of harmful patterns of use. ConclusionsThere has probably been a modest increase in the THC content of cannabis, but changing patterns of cannabis use have probably made a larger contribution to any increase in rates of cannabis-related problems among young Australian adults. ImplicationsBetter data on the THC content of cannabis, the extent of cannabis-related problems and the ability of users to titrate the dose of cannabis would contribute to more informed debate.

Phospholipase participation in cannabinoid-induced release of free arachidonic acid

The exposure of cells in culture to cannabinoids results in a rapid and significant mobilization of phospholipid bound arachidonic acid. In vivo, this effect has been observed as a rise in eicosanoid tissue levels that may account for some of the pharmacological actions of Δ 9-tetrahydrocannabinol (THC), the major psychoactive cannabinoid. Fluoroaluminate pretreatment of mouse peritoneal cells potently reduced the cannabinoid response, while promoting arachidonate release on its own, consistent with earlier observations that this effect may be a receptor/G-protein-mediated process. Further support for receptor mediation was the demonstration of saturable, high-affinity cannabinoid binding in these cells. THC potency was reduced in the presence of ethanol, and was accompanied by significant increases in phosphatidylethanol (PdEt) levels, a unique product of phospholipase D (PLD) activity. THC-dependent arachidonate release was reduced partially in similar amounts by either propranolol or wortmannin, further implicating PLD as a mediator of THC action. A central role for diacylglyceride (DAG), a secondary product of PLD metabolism, in this THC-induced process, both as a source of arachidonate and as a stimulator of protein kinase C (PKC), is supported by the data in this report. Cells exposed to phorbol ester for 18 hr prior to THC challenge became less responsive, indicating a possible role for PKC. The involvement of PKC further suggests participation by phospholipase A 2 (PLA 2) whose activity may be regulated by the former. Treatment of cells with interleukin-1α, an agent known to elevate PLA 2 levels, caused an increase in the THC response, supporting a role for this enzyme in the release reaction. Direct evidence, by immunoblotting, for the activation and phosphorylation of PLA 2 by THC was also obtained. In summary, the evidence presented in this report indicates that THC-induced arachidonic acid release occurs through a series of events that are consistent with a receptor-mediated process involving the stimulation of one or more phospholipases.