The Effectiveness of Common Cannabis Products for Treatment of Nausea.

GOALS: We measure for the first time how a wide range of cannabis products affect nausea intensity in actual time. BACKGROUND: Even though the Cannabis plant has been used to treat nausea for millennia, few studies have measured real-time effects of common and commercially available cannabis-based products. STUDY: Using the Releaf App, 886 people completed 2220 cannabis self-administration sessions intended to treat nausea between June 6, 2016 and July 8, 2019. They recorded the characteristics of self-administered cannabis products and baseline symptom intensity levels before tracking real-time changes in the intensity of their nausea. RESULTS: By 1 hour postconsumption, 96.4% of people had experienced symptom relief with an average symptom intensity reduction of -3.85 points on a 0 to 10 visual analog scale (SD=2.45, d=1.85, P<0.001). Symptom relief was statistically significant at 5 minutes and increased with time. Among product characteristics, flower and concentrates yielded the strongest, yet similar results; products labeled as Cannabis indica underperformed those labeled as Cannabis sativa or hybrid; and joints were associated with greater symptom relief than pipes or vaporizers. In sessions using flower, higher tetrahydrocannbinol and lower cannabidiol were generally associated with greater symptom relief (eg, within 5 min). CONCLUSIONS: The findings suggest that the vast majority of patients self-selecting into cannabis use for treatment of nausea likely experience relief within a relative short duration of time, but the level of antiemetic effect varies with the characteristics of the cannabis products consumed in vivo. Future research should focus on longer term symptom relief, including nausea-free intervals and dosing frequency; the risks of consumption of medical cannabis, especially among high-risk populations, such as pregnant women and children; and potential interactions between cannabis, conventional antiemetics, other medications, food, tobacco, alcohol, and street drugs among specific patient populations.

The Effectiveness of Cannabis Flower for Immediate Relief from Symptoms of Depression.

Objective: Scientific research on how consumption of whole, natural Cannabis flower affects low mood and behavioral motivations more generally is largely nonexistent, and few studies to date have measured how common and commercially available Cannabis flower used in vivo may affect the experience of "depression" in real-time. Methods: We observed 1,819 people who completed 5,876 cannabis self-administration sessions using the ReleafApp™ between 06/07/2016 and 07/08/2019, with the goal of measuring real-time effects of consuming Cannabis flower for treating symptoms of depression. Results: On average, 95.8% of users experienced symptom relief following consumption with an average symptom intensity reduction of -3.76 points on a 0-10 visual analogue scale (SD = 2.64, d = 1.71, p <.001). Symptom relief did not differ by labeled plant phenotypes ("C. indica," "C. sativa," or "hybrid") or combustion method. Across cannabinoid levels, tetrahydrocannabinol (THC) levels were the strongest independent predictors of symptom relief, while cannabidiol (CBD) levels, instead, were generally unrelated to real-time changes in symptom intensity levels. Cannabis use was associated with some negative side effects that correspond to increased depression (e.g. feeling unmotivated) in up to 20% of users, as well as positive side effects that correspond to decreased depression (e.g. feeling happy, optimistic, peaceful, or relaxed) in up to 64% of users. Conclusions: The findings suggest that, at least in the short term, the vast majority of patients that use cannabis experience antidepressant effects, although the magnitude of the effect and extent of side effect experiences vary with chemotypic properties of the plant.

Multi-level selection, social signaling, and the evolution of human suffering gestures: The example of pain behaviors.

Pain suffering has been naturally selected to be experienced and expressed within a wider social system. The communication of pain improves group coordination and decision-making about engaging in resource dependent and potentially risky endeavors. Recent findings warrant the development of a cohesive framework for understanding the reciprocal nature of pain expression and individual and group-level outcomes that can generate novel predictions on the heuristical expression of human suffering in naturalistic and clinical settings.

Does ultrasociality really exist - and is it the best predictor of human economic behaviors?

We agree that human economic structures can be informed by comparative analyses; however, we do not agree with several of Gowdy & Krall's specific assertions, which may hinder the generative potential of their model. We discuss these limitations from both biological and economic perspectives, and offer an alternative explanation for the expression of human economic behaviors based on individual optimization strategies.

Task specificity and the impact on both the individual and group during the formation of groups.

We agree with aspects of Baumeister et al.'s view that shared identities are necessary during initial stages of group formation. In contrast to their analysis, however, we provide evidence that the value of self-differentiation depends more on the task itself than on the stage of group development and challenge the authors to focus on the functions of the group.

Facial expression judgments support a socio-relational model, rather than a negativity bias model of political psychology.

Self-reported opinions and judgments may be more rooted in expressive biases than in cognitive processing biases, and ultimately operate within a broader behavioral style for advertising the capacity - versus the trustworthiness - dimension of human reciprocity potential. Our analyses of facial expression judgments of likely voters are consistent with this thesis, and directly contradict one major prediction from the authors' "negativity-bias" model.

Subtle variation in ambient room temperature influences the expression of social cognition.

Social signaling models predict that subtle variation in climatic temperature induces systematic changes in expressed cognition. An experiment showed that perceived room temperature was associated with variability in self-descriptions, social reactions of others, and desiring differing types of social networks. The findings reflect the tendency to inflate capacity demonstrations in warmer climates as a result of the social networking opportunities they enable.

Understanding feeling "high" and its role in medical cannabis patient outcomes.

Introduction: We measure for the first time the associations between subjective patient experiences of feeling "high" and treatment outcomes during real-time Cannabis flower consumption sessions. Methods: Our study uses data from the mobile health app, Releaf App™, through which 1,882 people tracked the effects of Cannabis flower on a multitude of health conditions during 16,480 medical cannabis self-administration sessions recorded between 6/5/2016 and 3/11/2021. Session-level reported information included plant phenotypes, modes of administration, potencies, baseline and post-administration symptom intensity levels, total dose used, and real-time side effect experiences. Results: Patients reported feeling high in 49% of cannabis treatment sessions. Using individual patient-level fixed effects regression models and controlling for plant phenotype, consumption mode, tetrahydrocannabinol (THC) and cannabidiol (CBD) potencies, dose, and starting symptom level, our results show that, as compared to sessions in which individuals did not report feeling high, reporting feeling high was associated with a 7.7% decrease in symptom severity from a mean reduction of -3.82 on a 0 to 10 analog scale (coefficient = -0.295, p < 0.001) with evidence of a 14.4 percentage point increase (p < 0.001) in negative side effect reporting and a 4.4 percentage point (p < 0.01) increase in positive side effect reporting. Tetrahydrocannabinol (THC) levels and dose were the strongest statistical predictors of reporting feeling high, while the use of a vaporizer was the strongest inhibitor of feeling high. In symptom-specific models, the association between feeling high and symptom relief remained for people treating pain (p < 0.001), anxiety (p < 0.001), depression (p < 0.01) and fatigue (p < 0.01), but was insignificant, though still negative, for people treating insomnia. Although gender and pre-app cannabis experience did not appear to affect the relationship between high and symptom relief, the relationship was larger in magnitude and more statistically significant among patients aged 40 or less. Discussion: The study results suggest clinicians and policymakers should be aware that feeling high is associated with improved symptom relief but increased negative side effects, and factors such as mode of consumption, product potency, and dose can be used to adjust treatment outcomes for the individual patient.

Intra-regional assortative sociality may be better explained by social network dynamics rather than pathogen risk avoidance.

Fincher & Thornhill's (F&T's) model is not entirely supported by common patterns of affect behaviors among people who live under varying climatic conditions and among people who endorse varying levels of (Western) religiosity and conservative political ideals. The authors' model is also unable to account for intra-regional heterogeneity in assortative sociality, which, we argue, can be better explained by a framework that emphasizes the differential expression of fundamental social cues for maintaining distinct social network structures.

Prejudicial behavior: more closely linked to homophilic peer preferences than to trait bigotry.

We disagree with Dixon et al. by maintaining that prejudice is primarily rooted in aversive reactions toward out-group members. However, these reactions are not indicative of negative attributes, such as trait bigotry, but rather normative homophily for peers with similar perceived attributes. Cognitive biases such as stereotype threat perpetuate perceptions of inequipotential and subsequent discrimination, irrespective of individuals' personality characteristics.

Neuronal deactivation is equally important for understanding emotional processing.

In their analyses of the neural correlates of discrete emotionality, Lindquist et al. do not consider the numerous drawbacks to inferring psychological processes based on currently available cognitive neurometric technology. The authors also disproportionately emphasize the relevance of neuronal activation over deactivation, which, in our opinion, limits the scope and utility of their conclusions.

The Effects of Consuming Cannabis Flower for Treatment of Fatigue.

Objectives: We measure for the first time how commercially available Cannabis flower products affect feelings of fatigue. Methods: A total of 1,224 people recorded 3,922 Cannabis flower self-administration sessions between June 6, 2016, and August 7, 2019, using the Releaf App. Usage sessions included real-time subjective changes in fatigue intensity levels prior to and following Cannabis consumption, Cannabis flower characteristics (labeled phenotype, cannabinoid potency levels), combustion method, and any potential experienced side effects. Results: On average, 91.94% of people experienced decreased fatigue following consumption with an average symptom intensity reduction of 3.48 points on a 0-10 visual analog scale (SD = 2.70, d = 1.60, p < 0.001). While labeled plant phenotypes ("C. indica," "C. sativa," or "hybrid") did not differ in symptom relief, people that used joints to combust the flower reported greater symptom relief than pipe or vaporizer users. Across cannabinoid levels, tetrahydrocannabinol, and cannabidiol levels were generally not associated with changes in symptom intensity levels. Cannabis use was associated with several negative side effects that correspond to increased feelings of fatigue (e.g., feeling unmotivated, couch-locked) among a minority of users (<24% of users), with slightly more users (up to 37%) experiencing a positive side effect that corresponds to increased energy (e.g., feeling active, energetic, frisky, or productive). Conclusions: The findings suggest that the majority of patients experience decreased fatigue from consumption of Cannabis flower consumed in vivo, although the magnitude of the effect and extent of side effects experienced likely vary with individuals' metabolic states and the synergistic chemotypic properties of the plant.

Current states of opinion and future directions on the epidemiology of sex differences in human pain.

One of the most commonly neglected findings in the human pain literature is the observation of sex differences in the mechanisms that support the phenotypic expression of pain. The present commentary describes an assessment of the prevalence of observed sex differences in various pain processes, and of how expert pain researchers interpret the epidemiology and, hence, the proximate and ultimate causes of such differences. Forty-two pain investigators completed an anonymous survey on the epidemiology of sex differences in the human pain experience. Investigator responses indicated that sex differences are pervasive across various areas of pain research, that sex differences are particularly pronounced in the area of situational influences on pain behaviors, and that contemporary pain researchers largely disagree on the epidemiology of, and hence, proximate and ultimate causes of the differences. The relevance of social situational factors on sex differences in pain behaviours is discussed in the context of evolutionary, developmental, social psychology and pain sensory systems that may function, in part, for regulating interpersonal intimacy.

Sex differences in salivary cortisol, alpha-amylase, and psychological functioning following Hurricane Katrina.

The study examines group and individual differences in psychological functioning and hypothalamic-pituitary-adrenal and sympathetic nervous system (SNS) activity among adolescents displaced by Hurricane Katrina and living in a U.S. government relocation camp (n = 62, ages 12-19 years) 2 months postdisaster. Levels of salivary cortisol, salivary alpha-amylase, depression, anxiety, distress, aggression, and self-esteem for this group were contrasted with a demographically matched no-trauma control group (n = 53). Results revealed that hurricane exposure and SNS activity moderated the relations between lower cortisol and higher internalizing behaviors. Sex-related differences were observed in behavioral adjustment and stress regulation. Implications of sex differences in biobehavioral adjustment to loss, displacement, and relocation are discussed in relation to evolutionary and developmental theory.

Alleviative effects of Cannabis flower on migraine and headache.

OBJECTIVE: Few studies to date have measured the real-time effects of consumption of common and commercially available Cannabis products for the treatment of headache and migraine under naturalistic conditions. This study examines, for the first time, the effectiveness of using dried Cannabis flower, the most widely used type of Cannabis product in the United States, in actual time for treatment of headache- and migraine-related pain and the associations between different product characteristics and changes in symptom intensity following Cannabis use. METHODS: Between 06/10/2016 and 02/12/2019, 699 people used the Releaf Application to record real-time details of their Cannabis use, including product characteristics and symptom intensity levels prior to and following self-administration; data included 1910 session-level attempts to treat headache- (1328 sessions) or migraine-related pain (582 sessions). Changes in headache- or migraine-related pain intensity were measured on a 0-10 scale prior to, and immediately, following Cannabis consumption. RESULTS: Ninety-four percent of users experienced symptom relief within a two-hour observation window. The average symptom intensity reduction was 3.3 points on a 0-10 scale (standard deviation = 2.28, Cohen's d = 1.58), with males experiencing greater relief than females (P < 0.001) and a trend that younger users (< 35 years) experience greater relief than older users (P = 0.08). Mixed effects regression models showed that, among the known (i.e., labeled) product characteristics, tetrahydrocannabinol levels 10% and higher are the strongest independent predictors of symptom relief, and this effect is particularly prominent in headache rather than migraine sufferers (P < 0.05), females (P < 0.05) and younger users (P < 0.001). Females and younger users also appear to gain greater symptom relief from flower labeled as "C. indica" rather than "C. sativa" or other hybrid strains. CONCLUSION: These results suggest that whole dried Cannabis flower may be an effective medication for treatment of migraine- and headache-related pain, but the effectiveness differs according to characteristics of the Cannabis plant, the combustion methods, and the age and gender of the patient.

The effectiveness of inhaled Cannabis flower for the treatment of agitation/irritability, anxiety, and common stress.

BACKGROUND: An observational research design was used to evaluate which types of commonly labeled Cannabis flower product characteristics are associated with changes in momentary feelings of distress-related symptoms. METHODS: We used data from 2306 patient-directed cannabis administration sessions among 670 people who used the real-time Cannabis effects recording software, Releaf App, between June 6, 2016, and February 23, 2019, for tracking the effects of Cannabis flower consumption. Fixed effects multivariable panel regression techniques were used to establish overall relief by symptom type and to determine which labeled product characteristics (e.g., subspecies/subtype, inhalation method, and major cannabinoid contents) showed the strongest correlation with changes in momentary feelings of agitation/irritability, anxiety, and stress, along with experienced side effects. RESULTS: In total, a decrease in symptom intensity levels was reported in 95.51% of Cannabis usage sessions, an increase in 2.32% of sessions, and no change in 2.16% of sessions. Fixed effects models showed, on average, respondents recorded a maximum symptom intensity reduction of 4.33 points for agitation/irritability (SE = 0.20, p < 0.01), 3.47 points for anxiety (SE = 0.13, p < 0.01), and 3.98 for stress (SE = 0.12, p < 0.01) on an 11-point visual analog scale. Fixed effects regressions showed that, controlling for time-invariant user characteristics, mid and high tetrahydrocannabinol (THC) levels were the primary independent predictor of increased symptom relief, and that when broken out by symptom type, this effect was only statistically significant for our largest sample of users, those reporting anxiety rather than agitation/irritability or stress. Cannabidiol (CBD) levels were generally not associated with changes in symptom intensity levels. In a minority of cannabis use sessions (< 13%), cannabis users reported anxiogenic-related negative side effects (e.g., feeling anxious, irritable, paranoid, rapid pulse, or restless), whereas in a majority of sessions (about 66%), users reported positive anxiolytic side effects (e.g., feeling chill, comfy, happy, optimistic, peaceful, or relaxed). CONCLUSIONS: The findings suggest the majority of patients in our sample experienced relief from distress-related symptoms following consumption of Cannabis flower, and that among product characteristics, higher THC levels were the strongest predictors of relief.

The Therapeutic Effectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model.

BACKGROUND: Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring 'Cannabis' pharmacodynamics. We used the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model to measure the effect of "full-spectrum" whole plant extracted hemp oil on chronic neuropathic pain sensitivity in mice. METHODS: Male BALBc mice were submitted to the FRICT-ION chronic neuropathic pain model with oral insertion through an incision in the buccal/cheek crease of 3 mm of chromic gut suture (4-0). The suture, wedged along the V2 trigeminal nerve branch, creates a continuous irritation that develops into secondary mechanical hypersensitivity on the snout. Von Frey filament stimuli on the mouse whisker pad was used to assess the mechanical pain threshold from 0-6 h following dosing among animals (n = 6) exposed to 5 µL of whole plant extracted hemp oil combined with a peanut butter vehicle (0.138 mg/kg), the vehicle alone (n = 3) 7 weeks post-surgery, or a naïve control condition (n = 3). RESULTS: Mechanical allodynia was alleviated within 1 h (d = 2.50, p < 0.001) with a peak reversal effect at 4 h (d = 7.21, p < 0.001) and remained significant throughout the 6 h observation window. There was no threshold change on contralateral whisker pad after hemp oil administration, demonstrating the localization of anesthetic response to affected areas. CONCLUSION: Future research should focus on how whole plant extracted hemp oil affects multi-sensory and cognitive-attentional systems that process pain.

Using recreational cannabis to treat insomnia: Evidence from over-the-counter sleep aid sales in Colorado.

This study seeks to understand whether people substitute between recreational cannabis and conventional over-the-counter (OTC) sleep medications. UPC-level grocery store scanner data in a multivariable panel regression design were used to compare the change in the monthly market share of sleep aids with varying dispensary-based recreational cannabis access (existence, sales, and count) in Colorado counties between 12/2013 and 12/2014. We measured annually-differenced market shares for sleep aids as a portion of the overall OTC medication market, thus accounting for store-level demand shifts in OTC medication markets and seasonality, and used the monthly changes in stores' sleep aid market share to control for short-term trends. Relative to the overall OTC medication market, sleep aid market shares were growing prior to recreational cannabis availability. The trend reverses (a 236% decrease) with dispensary entry (-0.33 percentage points, 95% CI -0.43 to -0.24, p < 0.01) from a mean market share growth of 0.14 ±â€¯0.97. The magnitude of the market share decline increases as more dispensaries enter a county and with higher county-level cannabis sales. The negative associations are driven by diphenhydramine- and doxylamine-based sleep aids rather than herbal sleep aids and melatonin. These findings support survey evidence that many individuals use cannabis to treat insomnia, although sleep disturbances are not a specific qualifying condition under any U.S. state-level medical cannabis law. Investigations designed to measure the relative effectiveness and side effect profiles of conventional OTC sleep aids and cannabis-based products are urgently needed to improve treatment of sleep disturbances while minimizing potentially serious negative side effects.

The effectiveness of self-directed medical cannabis treatment for pain.

The prior medical literature offers little guidance as to how pain relief and side effect manifestation may vary across commonly used and commercially available cannabis product types. We used the largest dataset in the United States of real-time responses to and side effect reporting from patient-directed cannabis consumption sessions for the treatment of pain under naturalistic conditions in order to identify how cannabis affects momentary pain intensity levels and which product characteristics are the best predictors of therapeutic pain relief. Between 06/06/2016 and 10/24/2018, 2987 people used the ReleafApp to record 20,513 cannabis administration measuring cannabis' effects on momentary pain intensity levels across five pain categories: musculoskeletal, gastrointestinal, nerve, headache-related, or non-specified pain. The average pain reduction was -3.10 points on a 0-10 visual analogue scale (SD = 2.16, d = 1.55, p < .001). Whole Cannabis flower was associated with greater pain relief than were other types of products, and higher tetrahydrocannabinol (THC) levels were the strongest predictors of analgesia and side effects prevalence across the five pain categories. In contrast, cannabidiol (CBD) levels generally were not associated with pain relief except for a negative association between CBD and relief from gastrointestinal and non-specified pain. These findings suggest benefits from patient-directed, cannabis therapy as a mid-level analgesic treatment; however, effectiveness and side effect manifestation vary with the characteristics of the product used.

The Association between Cannabis Product Characteristics and Symptom Relief.

Federal barriers and logistical challenges have hindered measurement of the real time effects from the types of cannabis products used medically by millions of patients in vivo. Between 06/06/2016 and 03/05/2018, 3,341 people completed 19,910 self- administrated cannabis sessions using the mobile device software, ReleafApp to record: type of cannabis product (dried whole natural Cannabis flower, concentrate, edible, tincture, topical), combustion method (joint, pipe, vaporization), Cannabis subspecies (C. indica and C. sativa), and major cannabinoid contents (tetrahydrocannabinol, THC; and cannabidiol, CBD), along with real-time ratings of health symptom severity levels, prior-to and immediately following administration, and reported side effects. A fixed effects panel regression approach was used to model the within-user effects of different product characteristics. Patients showed an average symptom improvement of 3.5 (SD = 2.6) on an 11-point scale across the 27 measured symptom categories. Dried flower was the most commonly used product and generally associated with greater symptom relief than other types of products. Across product characteristics, only higher THC levels were independently associated with greater symptom relief and prevalence of positive and negative side effects. In contrast, CBD potency levels were generally not associated with significant symptom changes or experienced side effects.