Cannabis Use During Early Pregnancy Following Recreational Cannabis Legalization.

Importance: It is unknown whether state recreational cannabis legalization (RCL) is related to increased rates of prenatal cannabis use or whether RCL-related changes vary with cannabis screening methods or the local policy environment. Objective: To test whether RCL in California was associated with changes in prenatal cannabis use rates, whether changes were evident in both self-report and urine toxicology testing, and whether rates varied by local policies banning vs allowing adult-use retailers post-RCL. Design, Setting, and Participants: This population-based time-series study used data from pregnancies in Kaiser Permanente Northern California universally screened for cannabis use during early pregnancy by self-report and toxicology testing from January 1, 2012, to December 31, 2019. Analyses were conducted from September 2022 to August 2024. Exposures: California state RCL passage (November 9, 2016) and implementation of legal sales (January 1, 2018) were examined with a 1-month lag. Local policies allowing vs banning medical retailers pre-RCL and adult-use retailers post-RCL were also examined. Main Outcomes and Measures: Any prenatal cannabis use was based on screening at entrance to prenatal care (typically at 8-10 weeks' gestation) and defined as (1) a positive urine toxicology test result or self-report, (2) a positive urine toxicology test result, or (3) self-report. Interrupted time series models were fit using Poisson regression, adjusting for age, race and ethnicity, and neighborhood deprivation index. Results: The sample of 300 993 pregnancies (236 327 unique individuals) comprised 25.9% Asian individuals, 6.4% Black individuals, 26.0% Hispanic individuals, 37.7% White individuals, and 4.1% individuals of other, multiple, or unknown race, with a mean (SD) age of 30.3 (5.4) years. Before RCL implementation, rates of prenatal cannabis use rose steadily from 4.5% in January 2012 to 7.1% in January 2018. There was no change in use rates at the time of RCL passage (level change rate ratio [RR], 1.03; 95% CI, 0.96-1.11) and a statistically significant increase in rates in the first month after RCL implementation, increasing to 8.6% in February 2018 (level change RR, 1.10; 95% CI, 1.04-1.16). Results were similar when defining prenatal cannabis use by (1) a toxicology test or (2) self-report. In local policy analyses, the post-RCL implementation increase in use was only found among those in jurisdictions allowing adult-use cannabis retailers (allowed RR, 1.21; 95% CI, 1.10-1.33; banned RR, 1.01; 95% CI, 0.93-1.10). Conclusions and Relevance: In this time-series study, RCL implementation in California was associated with an increase in rates of cannabis use during early pregnancy, defined by both self-report and toxicology testing, driven by individuals living in jurisdictions that allowed adult-use retailers.

Implications of Prenatal Cannabis Exposure on Childhood Neurodevelopmental Outcomes: A Summary of the Clinical Evidence.

Importance: Cannabis is commonly used by pregnant patients for alleviation of pregnancy-associated symptoms. Multiple national medical associations have recommended against prenatal cannabis use, yet misinformation regarding its safety and efficacy remains prevalent in public discourse. Effective and evidence-based patient counseling on prenatal cannabis use requires a thorough understanding of the existing data on fetal neurodevelopment. Objective: The aim of this study was to summarize the existing clinical literature on the impacts of intrauterine cannabis exposure on offspring neurodevelopment. Evidence Acquisition: Articles were identified via literature search in PubMed and OVID; relevant articles were reviewed. Results: Limited data have shown associations between intrauterine cannabis exposure and (1) increased startles and difficulty with consolation in the neonatal period, (2) memory challenges, verbal reasoning challenges, and diminished academic performance during early childhood, and (3) inattention, hyperactivity, and aggression during early childhood. Further research with large and diverse samples that use objective measures of cannabis use across multiple time points in pregnancy is required to assess causation, the true extent of impacts, and dose-dependent effects. Conclusions and Relevance: The existing clinical data regarding the impacts of prenatal cannabis use on fetal neurodevelopment are limited by important confounders like genetic predisposition, concomitant tobacco and other substance use during pregnancy, and low socioeconomic status. However, the theoretical and demonstrated associations between prenatal cannabis use and adverse neurodevelopmental outcomes are compelling enough to warrant complete abstinence during pregnancy, pending further research. Providers can utilize this summary to offer data-driven guidance on prenatal cannabis use for pregnant patients.

Preparation of a nanoemulsion containing active ingredients of cannabis extract and its application for glioblastoma: in vitro and in vivo studies.

Recently, the anti-tumor effects of cannabis extract on various cancers have attracted the attention of researchers. Here, we report a nanoemulsion (NE) composition designed to enhance the delivery of two active components in cannabis extracts (∆9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)) in an animal model of glioblastoma. The efficacy of the NE containing the two drugs (NED) was compared with the bulk drugs and carrier (NE without the drugs) using the C6 tumor model in rats. Hemocompatibility factors (RBC, MCV, MCH, MCHC, RDW, PPP, PT and PTT) were studied to determine the potential in vivo toxicity of NED. The optimized NED with mean ± SD diameter 29 ± 6 nm was obtained. It was shown that by administering the drugs in the form of NED, the hemocompatibility increased. Cytotoxicity studies indicated that the NE without the active components (i.e. mixture of surfactants and oil) was the most cytotoxic group, while the bulk group had no toxicity. From the in vivo MRI and survival studies, the NED group had maximum efficacy (with ~4 times smaller tumor volume on day 7 of treatment, compared with the control. Also, survival time of the control, bulk drug, NE and NED were 9, 4, 12.5 and 51 days, respectively) with no important adverse effects. In conclusion, the NE containing cannabis extract could be introduced as an effective treatment in reducing brain glioblastoma tumor progression.

Is cannabis a slippery slope? Associations between psychological dysfunctioning, other substance use, and impaired driving, in a sample of active cannabis users.

Cannabis is a gateway drug that can lead to the engagement of other substances. Psychological dysfunctioning and dependence have been highlighted as primary components to substance misuse. The purpose of this study was to investigate what aspects of cannabis use and psychological dysfunctioning are associated with the engagement of other substances and impaired driving. Subject to screening, 200 active adult cannabis users completed an online survey. Existing data involving non-cannabis users (N = 833) were also implemented as comparative data. The comparisons suggested that cannabis users were far more likely to have used other drugs in the past 12 months, compared to non-cannabis users. Bivariate correlations and multiple regressions indicated that the degree of cannabis use and likely dependence, psycho-social motives for using cannabis, emotion dysregulation, and psychopathology were positively associated with the frequency of using and driving on other substances. Finally, an ANOVA demonstrated that outside of age, there were no apparent differences in substance use behaviours, motives for using cannabis, and psychological dysfunction, between medicinal and black-market cannabis users. These findings highlight the potential benefits of incorporating self-regulatory concepts into current road safety initiatives, which aim to reduce the interconnected issue of substance misuse and impaired driving behaviours.

A 10-year trend in cannabis potency (2013-2022) in different geographical regions of the United States of America.

Background: The prevalence of cannabis as the most commonly used illicit substance in the United States and around the globe is well-documented. Studies have highlighted a noticeable uptrend in the potency of cannabis in the United states. This report examines the concentration of cannabinoids in illicit cannabis samples seized by the United States Drug Enforcement Administration (DEA) over the last 10 years (2013-2022). Methods: Samples received during the course of study (2013-2022) were categorized based on the geographical region where collected, as Western Region, Midwest Region, Northeast Region, South East Region, Southern Region as well as Alaska and Hawaii. These samples were processed for analysis using a validated gas chromatography with flame ionization detector method. Results: The data showed that the cannabinoids profile of all high Δ9-THC cannabis samples, regardless of the state or region from which the samples are seized or the state from which the sample is produced under a state medical marijuana program, is basically the same with the major cannabinoid being Δ9-THC (>10% for most samples) and all other cannabinoids with less than 0.5%, with the exception of CBG (<1%) and CBN (<1%). Conclusion: Overall, it appears the cannabinoids profile is controlled by the genetics of the plant and is not affected much by the geographical location in which the plants are cultivated.

Functions of Hemp-Induced Exosomes against Periodontal Deterioration Caused by Fine Dust.

Although fine dust is linked to numerous health issues, including cardiovascular, neurological, respiratory, and cancerous diseases, research on its effects on oral health remains limited. In this study, we investigated the protective effects of mature hemp stem extract-induced exosomes (MSEIEs) on periodontal cells exposed to fine dust. Using various methods, including microRNA profiling, PCR, flow cytometry, immunocytochemistry, ELISA, and Alizarin O staining, we found that MSE treatment upregulated key microRNAs, such as hsa-miR-122-5p, hsa-miR-1301-3p, and hsa-let-7e-5p, associated with vital biological functions. MSEIEs exhibited three primary protective functions: suppressing inflammatory genes while activating anti-inflammatory ones, promoting the differentiation of periodontal ligament stem cells (PDLSCs) into osteoblasts and other cells, and regulating LL-37 and MCP-1 expression. These findings suggest that MSEIEs have potential as functional biomaterials for applications in pharmaceuticals, cosmetics, and food industries.

Cannabis-Derived Product Types, Flavors, and Compound Types From an E-Commerce Website.

Importance: Cannabis-derived products (CDPs) are widely available and diverse. A classification of product and flavor types is necessary to establish a foundation for comparative research, although research aiming to classify cannabis in its variety of products, flavors, and cannabinoid compounds based on public online e-commerce data is lacking. Objective: To analyze data from a large cannabis e-commerce marketplace to identify and characterize cannabis product types, flavors, and compound types. Design, Setting, and Participants: This qualitative study was conducted in 2 phases: (1) data mining of the cannabis e-commerce website Weedmaps for product listings in the US between September 1 and November 30, 2023 and (2) grouping CDPs into product, flavor, and cannabinoid compound categories. Exposures: Cannabis product listings. Main Outcomes and Measures: Product listings and descriptions were extracted from the platform. Coding was performed for specific product characteristics, routes of administration (ROAs), and characterization of flavors. Results: A total of 573 854 unique US CDP sales listings from the platform were collected; after removing 72 842 nonconsumable items, 501 012 were analyzed. Product ROAs included multisystem (205 637 [41.04%]), respiratory (185 296 [36.98%]), digestive (98 941 [19.75%]), epidermal (9487 [1.89%]), and oral (1651 [0.33%]). Nearly half (210 575 [42.03%]) of all product listings included at least 1 flavor, with 247 762 instances of flavors. The 3 most common flavors were lemon (22 106 [8.92%]), cake (19 463 [7.86%]), and strawberry (13 961 [5.63%]). The most common cannabinoid compound type was Δ9-tetrahydrocannabinol (54 699 [63.30%]). Conclusions and Relevance: This qualitative study categorized more than half a million CDPs for product and flavor types. Results are needed for comparative studies on product and market availability and can help in assessing concerns about appealing characteristics. The results can also inform future market surveillance efforts aimed at identifying new and emerging products as cannabis policy continues to move toward greater legalization.

Cannabis use disorder: from neurobiology to treatment.

Cannabis has been legalized for medical and recreational purposes in multiple countries. A large number of people are using cannabis and some will develop cannabis use disorder (CUD). There is a growing recognition that CUD requires specific interventions. This Review will cover this topic from a variety of perspectives, with a particular emphasis on neurobiological findings and innovative treatment approaches that are being pursued. We will first describe the epidemiology and burden of disease of CUD, including risk factors associated with CUD (both in terms of general risk and genetic risk variants). Neurobiological alterations identified in brain imaging studies will be presented. Several psychosocial interventions that are useful for the management of CUD, including motivational enhancement therapy, behavioral and cognitive therapy, and contingency management, will be covered. Although no pharmacological interventions are yet approved for CUD, we present the most promising pharmacological interventions being tested.

Cannabis and Pain Management.

Family physicians are fielding questions about cannabis --particularly for the use of cannabis for treatment of pain. Like about every substance ingested to treat medical conditions, cannabis has risks and benefits. But regarding evidence-based practice and practice-based recommendations for patients about cannabis use, the cart is in front of the horse. Cannabis use is still illegal at a federal level and a Schedule 1 drug, but most states have challenged federal law by decriminalizing or legalizing cannabis for a variety of uses. Research is difficult due to this federal status as a Schedule 1 drug since federal funding is not readily available to support research. As a result, physicians have little to no guidance about the clinical usefulness of the product. This article explores what we know and what we are learning about cannabis, and the authors provide clinical guidance for patient care based on this evidence.

Cannabis Use during Pregnancy: An Update.

The use of cannabis during pregnancy has emerged as a mounting cause for concern due to its potential adverse consequences on both the mother and her offspring. This review will focus on the dangers associated with prenatal exposure to cannabis, particularly those related to neurodevelopment. It will also discuss the features of maternal and placental functioning that are likely to have long-term effects on the offspring's development. The most pertinent and up-to-date materials can be found through a literature search. The literature emphasizes the substantial hazards associated with prenatal exposure to cannabis. These include impairments in cognitive function and difficulties in behavior in this particular instance. Structural and functional alterations in the brain can be noticed in offspring. The use of cannabis has been associated with an increased likelihood of experiencing pregnancy-related complications, such as giving birth prematurely and having a baby with a low birth weight. Additionally, it has been connected to potential negative effects on mental and emotional well-being. Studies have shown that when a pregnant woman is exposed to cannabis, it can negatively impact the functioning of the placenta and the growth of the fetus. This might potentially contribute to the development of placental insufficiency and restricted growth in the womb. Longitudinal studies reveal that children who were exposed to cannabis in the womb experience additional long-term developmental challenges, such as decreased cognitive abilities, reduced academic performance, and behavioral issues. In order to address the problem of cannabis usage during pregnancy, it is essential to adopt a comprehensive and coordinated strategy. This method should integrate and synchronize public health policy, education, and research initiatives. By implementing these targeted strategies, it is possible to mitigate potential health and welfare concerns for both present and future generations.

Cannabis Use and Cannabidiol Modulate HIV-Induced Alterations in TREM2 Expression: Implications for Age-Related Neuropathogenesis.

Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neuroinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized that TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. EcoHIV-infected wildtype (WT) and TREM2R47H mutant mice were used to study HIV's impact on TREM2 and behavior. TREM2 and related gene expressions were examined in monocyte-derived macrophages (MDMs) from PWH (n = 42) and people without HIV (PWoH; n = 19) with varying cannabis use via RNA sequencing and qPCR. Differences in membrane-bound and soluble TREM2 (sTREM2) were evaluated using immunocytochemistry (ICC) and ELISA. EcoHIV increased immature and C-terminal fragment forms of TREM2 in WT mice but not in TREM2R47H mice, with increased IBA1 protein in TREM2R47H hippocampi, correlating with worse memory test performance. TREM2 mRNA levels increased with age in PWoH but not in PWH. Cannabidiol (CBD) treatment increased TREM2 mRNA alone and with IL1ß. RNA-seq showed the upregulation of TREM2-related transcripts in cannabis-using PWH compared to naïve controls. IL1ß increased sTREM2 and reduced membrane-bound TREM2, effects partially reversed by CBD. These findings suggest HIV affects TREM2 expression modulated by cannabis and CBD, offering insights for therapeutic strategies.

Cannabis Use and Anesthesia.

Consistent evidence supporting the use of cannabinoids for management of acute pain is lacking. A small number of observational studies suggest cannabinoid use is associated with reduced opioid use but pain scores remain unchanged. The majority of randomized trials involving a variety of cannabinoid compounds have shown no benefit for acute pain. Chronic cannabis users may be at increased risk of experiencing elevated levels of acute pain and these individuals may require greater quantities of opioids compared to non-cannabis users. There is also evidence suggesting that chronic, high-dose cannabis users may be at increased risk of perioperative cardiovascular complications.

Early Maternal Prenatal Cannabis Use and Child Developmental Delays.

Importance: Maternal prenatal cannabis use is associated with adverse neonatal health effects, yet little is known about its association with child developmental outcomes. Objective: To evaluate associations between maternal prenatal cannabis use in early pregnancy and child early developmental delays. Design, Setting, and Participants: This cohort study included 119 976 children born to 106 240 unique individuals between January 2015 and December 2019 and followed up to aged 5.5 years or younger (through December 31, 2021) at Kaiser Permanente Northern California. Individuals were screened for prenatal cannabis use via self-report and urine toxicology at entrance into prenatal care (approximately 8- to 10-weeks' gestation). Data were analyzed from February 2023 to March 2024. Exposure: Maternal prenatal cannabis use defined as any use (self-reported or by urine toxicology testing) and use frequency. Main Outcomes: Early developmental delays (speech and language disorders, motor delays, global delays) in children up to age 5.5 years defined by International Statistical Classification of Diseases and Related Health Problems, Ninth Revision and Tenth Revision diagnoses codes ascertained from electronic health records. Results: In this cohort of 119 976 pregnancies among 106 240 unique pregnant individuals, there were 29 543 Hispanic pregnancies (24.6%), 6567 non-Hispanic Black pregnancies (5.5%), 46 823 non-Hispanic White pregnancies (39.0%), 12 837 pregnancies (10.7%) to individuals aged 24 years or younger, and 10 365 pregnancies (8.6%) to individuals insured by Medicaid. Maternal prenatal cannabis use was documented for 6778 pregnancies (5.6%). Daily maternal prenatal cannabis use was reported for 618 pregnancies (0.5%), weekly for 722 pregnancies (0.6%), and monthly or less for 1617 pregnancies (1.3%). No association was observed between maternal prenatal cannabis use and child speech and language disorders (HR, 0.93; 95% CI, 0.84-1.03), global developmental delays (HR, 1.04; 95% CI, 0.68-1.59), or motor delays (HR, 0.86; 95% CI, 0.69-1.06). No association was detected between the frequency of maternal prenatal cannabis use and child early developmental delays. Conclusions and Relevance: In this cohort study, maternal prenatal cannabis use was not associated with an increased risk of child early developmental delays. Future research is needed to assess different patterns of cannabis use throughout pregnancy. Given the association between maternal prenatal cannabis use and other adverse outcomes, pregnant individuals should be educated on those risks.

Bioefficiency of microencapsulated hemp leaf phytonutrient-based extracts to enhance in vitro rumen fermentation and mitigate methane production.

The objective was to assess the supplementation with microencapsulation of hemp leaf extract (mHLE) utilized as a rumen enhancer on in vitro rumen fermentation and to enhance the bioavailability of active compounds for antimicrobial action, particularly in protozoa and methanogen populations. The feed treatments were totally randomized in the experimental design, with different levels of mHLE diet supplemented at 0, 4, 6 and 8% of total DM substrate and added to an R:C ratio of 60:40. During fermentation, gas kinetics production, nutrient degradability, ammonia nitrogen concentration, volatile fatty acid (VFA) profiles, methane production, and the microbial population were measured. The supplemented treatment at 6% of total DM substrate affected reductions in gas kinetics, cumulative gas production, and volatile fatty acid profiles, especially the acetate and acetate to propionate ratio. Whereas propionate proportion and total volatile fatty acid concentration were enhanced depending on the increase of nutrients in vitro dry matter degradability (IVDMD) after 12 h of post-fermentation at a R:C ratio of 60:40 (P < 0.05). Consequently, mHLE addition resulted in optimal ruminal pH and increased nutrient degradability, followed by ammonia nitrogen concentrations (P < 0.05), which were enhanced by dominant cellulolytic bacteria, particularly Ruminococcus albus and Ruminococcus flavefaciens, which showed the highest growth rates in the rumen ecology. Therefore, mHLE, a rich phytonutrient feed additive, affected the methanogen population, reduced the calculated methane production and can be a potential supplement in the ruminant diet.

Regulatory Landscape of Cannabis Warning Labels in US States with Legal Retail Nonmedical Cannabis, 2024.

Objectives. To characterize regulatory practices related to nonmedical cannabis warning labels in states across the United States that have legalized retail nonmedical cannabis. Methods. In March 2024, we conducted a content analysis of regulations for nonmedical cannabis warning labels required on product packages in 20 states where, as of March 2024, adults could legally purchase nonmedical cannabis in retail environments. For each state, we examined requirements related to warning label content and characteristics. Results. Required warning label content and characteristics varied widely across states. Only 2 states required a warning about mental health risks (10%) and 2 states required a warning for high potency products on risk of psychosis (10%). No states required front-of-package warning placement, only 2 states required rotating warnings (10%), and 4 states required contrasting colors (20%). Warnings were often verbose (mean = 57 words), vague, and had small or no minimum font size. Conclusions. Opportunities exist for states to improve the alignment of their nonmedical cannabis warning label regulations with evidence that has been generated so far in cannabis effects, cannabis warning efficacy, and warning label design. (Am J Public Health. 2024;114(S8):S681-S684. https://doi.org/10.2105/AJPH.2024.307722).

Association of Local Cannabis Policy and Retail Availability With Cannabis Use and Problematic Cannabis Use Among Adolescents in Northern California.

Objectives. To examine whether local cannabis policies and retail availability are associated with cannabis use and problematic cannabis use (PCU) among adolescents in Northern California. Methods. The sample comprised adolescents aged 13 to 17 years screened for past-year cannabis use during well-child visits in 2021. Exposures included local bans on cannabis storefront retailers, policy protectiveness, and retail proximity and density. Outcomes included self-reported past-year cannabis use and PCU diagnoses. Modified Poisson regression models adjusted for sociodemographics. Results. The sample (n = 103 134) was 51.1% male with a median age of 15 years (interquartile range [IQR] = 14-16 years); 5.5% self-reported cannabis use, and 0.3% had diagnosed PCU. Adolescents had a lower prevalence of cannabis use in jurisdictions that banned storefront retailers (adjusted prevalence rate [APR] = 0.857; 95% confidence interval [CI] = 0.814, 0.903 vs allowed), banned delivery (APR = 0.751; 95% CI = 0.710, 0.795 vs allowed), or had more policy protections (APR range = 0.705-0.800). Lower PCU prevalence was also found among those in jurisdictions that banned (vs allowed) storefront retailers (APR = 0.786; 95% CI = 0.629, 0.983) or delivery (APR = 0.783; 95% CI = 0.616, 0.996). Longer drive time and lower density of storefront retailers were associated with a lower cannabis use prevalence. Conclusions. More protective cannabis policies and less retail availability were associated with a lower prevalence of adolescent cannabis use and PCU. (Am J Public Health. 2024;114(S8):S654-S663. https://doi.org/10.2105/AJPH.2024.307787).

Pneumothoraces Associated With Vaping Cannabis Concentrate.

Vaping-associated spontaneous pneumothorax (VASP) is a new diagnosis created to describe spontaneous pneumothorax associated with the use of vape devices. We describe a case of bilateral VASP in a previously healthy 15-year-old male who was vaping cannabis concentrate. This is the first case report of VASP involving the sole usage of cannabis concentrate. This patient reported vaping for only 6 months before initial presentation. As rates of vaping cannabis concentrate increase among adolescents, VASP should be considered in the differential diagnosis of chest pain in adolescents who vape nicotine or cannabis.

Unveiling the Potential of Phytocannabinoids: Exploring Marijuana's Lesser-Known Constituents for Neurological Disorders.

Cannabis sativa is known for producing over 120 distinct phytocannabinoids, with Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) being the most prominent, primarily in their acidic forms. Beyond Δ9-THC and CBD, a wide array of lesser-known phytocannabinoids, along with terpenes, flavonoids, and alkaloids, demonstrate diverse pharmacological activities, interacting with the endocannabinoid system (eCB) and other biological pathways. These compounds, characterized by phenolic structures and hydroxyl groups, possess lipophilic properties, allowing them to cross the blood-brain barrier (BBB) effectively. Notably, their antioxidant, anti-inflammatory, and neuro-modulatory effects position them as promising agents in treating neurodegenerative disorders. While research has extensively examined the neuropsychiatric and neuroprotective effects of Δ9-THC, other minor phytocannabinoids remain underexplored. Due to the well-established neuroprotective potential of CBD, there is growing interest in the therapeutic benefits of non-psychotropic minor phytocannabinoids (NMPs) in brain disorders. This review highlights the emerging research on these lesser-known compounds and their neuroprotective potential. It offers insights into their therapeutic applications across various major neurological conditions.

Geo-climatic factors co-drive the phenotypic diversity of wild hemp (Cannabis sativa L.) in the Potohar Plateau and Lesser Himalayas.

Hemp (Cannabis sativa L.) is an annual, and dioecious herb belonging to the Cannabaceae family. This plant is native to Central and Southeast Asia. The wild races of this species are commonly growing in Khyber Pakhtunkhwa and Punjab provinces, as well as in Islamabad, Pakistan. This study provides crucial insights into how environmental variables influence the wild hemp populations, which can be utilized in for conservation and breeding. The present study was aimed at evaluating the effects of key environmental factors such as altitude, geographical location, precipitation, relative humidity, maximum, minimum, and average temperature on 16 morpho-agronomic traits of a wild population of hemp growing in the Potohar Plateau and Lesser Himalayas. Our findings indicated that high relative humidity (> 64%), low average temperature (< 15 °C), intermediate average temperature (19-22 °C), and high average temperature (> 22 °C) played significant roles in determining the distribution pattern of the wild hemp. Correlation analysis demonstrated that average annual temperature contributed a higher percentage of variation in phenotypic diversity than geographic variables. Additionally, cluster analysis indicated three groups for the selected 35 populations. Clustering and Principal Component Analysis (PCA) of the morpho-agronomic traits indicated that group 1 from the Lesser Himalayas showed high relative humidity (> 64%) and low average temperature (< 15 °C). Conversely, Group 2 populations from the Potohar Plateau demonstrated intermediate average temperature (19-22 °C). There is an existence of Group 3 in the Potohar Plateau with a high average temperature (> 22 °C) compared to Group 1 and Group 2. Our examination highlights the complex interplay between ecological factors, and morphological attributes in native landraces of Cannabis sativa, giving significant insight into knowledge for preservation and breeding initiatives. A study of genetic diversity could complement morpho-agronomic traits in future research to learn more about how genetic variation affects environmental adaptation.