{"doi":"10.2139/ssrn.4771964","title":"Sex Differences in Inter-Temporal Decision Making and Cortical Thickness of the Orbitofrontal and Insula in Young Adult Cannabis Users: Evidence from 1111 Subjects","abstract":"<jats:p>BACKGROUNDCannabis use disorder (CUD) is associated with impulsive behaviors and risky decision making. To test for sex differences in the impact of cannabis use on risky decision making (DM) and their brain correlates, we employed cortical thickness analysis of the brain regions involved in intertemporal decision making (DM) namely bilateral orbitofrontal cortex (OFC) and insula in young adult nondependent cannabis users (CU) and age matched non-users (NU). We also examined their scores on the delay discounting task a measure of inter-temporal decision making.METHODSNeuroimaging analyses of previously collected data via the Human Connectome Project were performed on 608 CU and 503 age-matched NU. Cortical thickness analysis was performed on processed images from a high dimensional 3T connectome scanner. OFC and insula volumes and scores on the delay discounting test were compared between the groups and correlated within groups.RESULTSControlling alcohol use and intra-cranial volume, we found differences in cortical thickness between the 2 groups. Examining sex differences, the bilateral insula was significantly thinner in male CU compared to male NU. The OFC was thinner in both sexes relative to controls but in different subregions. Male CU had thinner R medial OFC and L lateral OFC, while female CU had thinner R lateral OFC and L medial and lateral OFC (relative to male and female NU, respectively). However, group X sex interaction was not significant and hence the effects of cannabis on the brain was not dimorphic. While male CU scored significantly lower on most of the items within delay discounting task (DD) female CU’s DD scores were within the range of the NU.The right insula positively correlated with the DD tasks AUC (area under the curve) in NU while the CU showed a trend. Male CU and not females showed significant correlations between insula and OFC thickness and frequency of cannabis use.CONCLUSIONSOur results demonstrate that cannabis use differentially affects decision making across the sexes. Cortical morphology mirrors these differential effects. CT scores and DM scores were correlated in nonusers. CU subjects did not show this relationship implying that thinner cortices and lower DD scores in males may be independent alterations and may be premorbid to cannabis use. These may lead to deficits in learning in later years.</jats:p>","journal":null,"year":null,"id":615908,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255922,"name":"Joan A. Camprodon","orcid":"0000-0003-1282-9257","position":1,"is_corresponding":false},{"id":1587692,"name":"Francesca  M. Filbey","orcid":null,"position":2,"is_corresponding":false},{"id":1587691,"name":"Alan  N. Francis","orcid":"0000-0001-8851-0758","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Sex Differences in Inter-Temporal Decision Making and Cortical Thickness of the Orbitofrontal and Insula in Young Adult Cannabis Users: Evidence from 1111 Subjects","abstract":"<jats:p>BACKGROUNDCannabis use disorder (CUD) is associated with impulsive behaviors and risky decision making. To test for sex differences in the impact of cannabis use on risky decision making (DM) and their brain correlates, we employed cortical thickness analysis of the brain regions involved in intertemporal decision making (DM) namely bilateral orbitofrontal cortex (OFC) and insula in young adult nondependent cannabis users (CU) and age matched non-users (NU). We also examined their scores on the delay discounting task a measure of inter-temporal decision making.METHODSNeuroimaging analyses of previously collected data via the Human Connectome Project were performed on 608 CU and 503 age-matched NU. Cortical thickness analysis was performed on processed images from a high dimensional 3T connectome scanner. OFC and insula volumes and scores on the delay discounting test were compared between the groups and correlated within groups.RESULTSControlling alcohol use and intra-cranial volume, we found differences in cortical thickness between the 2 groups. Examining sex differences, the bilateral insula was significantly thinner in male CU compared to male NU. The OFC was thinner in both sexes relative to controls but in different subregions. Male CU had thinner R medial OFC and L lateral OFC, while female CU had thinner R lateral OFC and L medial and lateral OFC (relative to male and female NU, respectively). However, group X sex interaction was not significant and hence the effects of cannabis on the brain was not dimorphic. While male CU scored significantly lower on most of the items within delay discounting task (DD) female CU’s DD scores were within the range of the NU.The right insula positively correlated with the DD tasks AUC (area under the curve) in NU while the CU showed a trend. Male CU and not females showed significant correlations between insula and OFC thickness and frequency of cannabis use.CONCLUSIONSOur results demonstrate that cannabis use differentially affects decision making across the sexes. Cortical morphology mirrors these differential effects. CT scores and DM scores were correlated in nonusers. CU subjects did not show this relationship implying that thinner cortices and lower DD scores in males may be independent alterations and may be premorbid to cannabis use. These may lead to deficits in learning in later years.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":"https://openalex.org/W4393171438","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"https://www.uspto.gov/ip-policy/copyright-policy/copyright-basics","oa_locations":[{"url":"http://dx.doi.org/10.2139/ssrn.4771964","host_type":"repository"},{"url":"http://dx.doi.org/10.2139/ssrn.4771964","host_type":"repository"}],"fields_of_study":["Epilepsy research and treatment","Memory and Neural Mechanisms","Functional Brain Connectivity Studies"],"mesh_terms":[],"keywords":["Insula","Orbitofrontal cortex","Cannabis","Psychology","Audiology","Neuroscience","Medicine","Psychiatry","Cognition","Prefrontal cortex"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Gender equality"},{"sdg_number":0,"sdg_label":"Peace, Justice and strong institutions"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T21:24:14.530701Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}