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Sex Differences in Mechanisms of Withdrawal and Recovery of Function in Emerging Adults with Heavy Cannabis Use

Award Number: R01DA063599
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Sex Differences in Mechanisms of Withdrawal and Recovery of Function in Emerging Adults with Heavy Cannabis Use - PROJECT SUMMARY/ABSRACT Regular, ongoing cannabis use is associated with persistent decrements in neuropsychological and behavioral (e.g., psychiatric, sleep) functioning. This is particularly a concern in vulnerable adolescents and young adults (AYAs) who undergo vast neurodevelopmental changes. It is unclear whether cessation of cannabis use, beyond withdrawal and after cannabinoids are no longer present in the body, result in recovery of neuropsychological and behavioral functioning. With increasing prevalence of frequent cannabis use and greater complexity of cannabis products and potency, though, improved cannabis measurement is needed. Use of biomarkers offers common metrics of cannabinoids despite this variability. Further, endocannabinoids (eCBs) are impacted by cannabis use and may represent another important factor in symptoms related to cannabis abstinence and ongoing recovery. Importantly, females are particularly vulnerable to the influence of cannabis and withdrawal symptoms, perhaps due to the sexually dimorphic nature of the endocannabinoid system, though consideration of sex-specific effects is limited. Prior studies that investigate the question of cannabis withdrawal and recovery of function suffer from too brief of monitoring periods with cannabinoids still detectable after the abstinence period, lack of measurement of objective toxicological or eCB biomarkers, and no consideration of sex. Therefore, we aim to characterize how sex-specific cannabinoid and eCB biomarkers predict neuropsychological, behavioral, and withdrawal outcomes over time during abstinence. We will recruit 220 AYA participants (ages 18-25; balanced by sex, 64% with heavy cannabis use) to undergo a 6-week monitored abstinence period with repeat toxicological, eCB, neuropsychological, and behavioral assessment, and with twice daily ecological momentary assessment. Using a multidimensional approach, we will investigate how toxicological and eCB biomarkers predict initial neuropsychological and behavioral symptoms during withdrawal (3 weeks after cessation of cannabis use) and potential for recovery after 6 weeks of abstinence. We will include sex as a moderator, given potential sex differences in the influence of cannabis and in endocannabinoid system functioning. AYA cannabis use is at historically high levels, with the most recent data indicating females report similar or higher levels of use than males. Greater strides in understanding the impact of and potential for recovery from frequent cannabis use is needed to motivate prevention and cessation efforts. Through combining toxicological and eCB biomarkers with repeat measurement over a 6-week closely monitored period, results may identify biomarker indicators of sex-specific decrements and recovery in AYAs during cannabis abstinence. Findings will advance sex-specific treatment/intervention targets through allowing for better treatment planning for anticipated withdrawal effects and to accelerate recovery from cannabis health consequences.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $734,188 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	1	7/10/2026	NEW	$734,188
														Subtotal = $734,188

Grand Total All Awards = $734,188

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Sex Differences in Mechanisms of Withdrawal and Recovery of Function in Emerging Adults with Heavy Cannabis Use

Award Number: R01DA063599

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/15/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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