One recent 20-year comparison of daily tobacco versus marijuana smokers showed only increased risk for periodontal disease with cannabis, whereas tobacco users had expected increases in lung, cardiac, and metabolic risk factors. Cannabis appears to have some anti-inflammatory properties; according to the National Academies report, there is insufficient evidence to support any conclusions about the impacts of cannabis on other immune functions. Interesting public health data suggest that there may be significant trends toward decreases in opioid overdose deaths in states with legalized cannabis,fewer overall traffic deaths after legalization, and reductions in pre-versus-post legalization Medicare expenditures on prescription analgesics, sedative-hypnotics, anxiolytics, and other agents.A separate but important consideration is whether a standard risk-benefit analysis makes sense for palliative care patients when contemplating cannabis. Risks of overgeneralization aside, most palliative care patients are NOT young people with unlimited life prospects who are early in their school years or social developmental trajectories, are NOT climbing career ladders, are NOT parenting small dependent children, or operating heavy industrial machinery. Thus, I would argue that this brief summary of safety risks should, in the palliative care clinical setting, be balanced against the exigencies of attempting to help patients achieve symptom relief in the context of serious illness, particularly if they are facing difficult symptoms not responsive to conventional treatments.In addition to those scientific and public policy matters outlined above, there are many other uncertainties facing the palliative care clinician and his/her patient contemplating cannabis grow racks. Chief among them is what the patient actually receives when he/she purchases medical marijuana at a dispensary: a recent small study of marijuana edibles showed accurate labeling in only 17%.The majority of products were ‘‘overlabeled’’ , while 23% were ‘‘underlabeled’’ . Geographic differences were noted as well, with Los Angeles dispensaries showing a significant inclination to underlabel.
FDA has recently published a report of its analysis of CBD products purchased over the internet, which showed most of the products to contain little or no active ingredient.These findings undermine a fundamental element of physician practice, namely the ability to identify and recommend specific, reliable doses of compounds. It should also be noted that under most of the state laws, physicians are not prescribing medical marijuana at all. Instead, they are asked to endorse, attest, or certify that in their professional judgment the patient has a disorder for which medical marijuana may have efficacy. This, too, is unfamiliar territory for many of us.Originally formulated over twenty years ago, and recently updated, the neural diathesis-stress model proposes that the hypothalamic-pituitary-adrenal axis is the central physiological mechanism linking psychosocial stress to the onset and exacerbation of schizophrenia and related psychotic disorders . A central tenet to this model is that individuals with increased vulnerability for psychosis are more sensitive to the effects of psychosocial stressors due to abnormalities within the HPA axis which in turn contribute to dopaminergic and glutamatergic abnormalities that eventually trigger expression of psychotic illness . In support of the model, accumulated evidence indicates that patients with psychosis exhibit elevated basal cortisol relative to healthy controls , but a blunted cortisol awakening response [CAR ], the latter thought to represent a distinct HPA axis component, independent of stress-induced cortisol secretion . More recently, these features have been reported among individuals who are at increased risk for psychosis due to clinical features and/or genetic liability . Moreover, at-risk individuals who later develop full psychosis show even greater increases in basal cortisol and pituitary volume , suggesting that increased HPA axis activity may signal risk for worsening illness. In parallel with this research, studies show that at-risk individuals report greater exposure and sensitivity to a range of psychosocial stressors, including major life events, childhood trauma, and minor daily stressors . However, there has been a paucity of studies examining the concordance between psychosocial stressor exposure/distress and HPA axis function; as such, the extent to which individuals on the psychosis spectrum exhibit ‘abnormal’ HPA axis responses to psychosocial stressors is unclear.
That is, the increases in basal cortisol observed in those with, and at-risk for, psychosis may represent either a ‘normal/ adaptive’ response to the high levels of psychosocial stressors reported in these populations , or hyperresponsivity of the HPA axis , characterised by an increase in cortisol greater than that expected in a healthy individual . Alternatively, the elevated basal cortisol levels observed may be partially independent of psychosocial stress exposure/distress , and instead reflect individual-level factors such as genetic predisposition to HPA axis hyperactivity or metabolic abnormalities , the latter being more common among individuals at clinical high-risk for psychosis , who present features consistent with the prodromal phase of illness. Two recent studies of at-risk individuals support the ‘increased concordance’ hypothesis: Using the experience sampling method, siblings of psychosis patients showed more pronounced increases in salivary cortisol in response to unpleasant events relative to controls , whilst a further study reported a stronger association between retrospectively-reported stressful life events and basal cortisol in CHR youth compared to controls . In contrast, lower cortisol responses during psychosocial stressor tasks have observed in CHR individuals and young adults with high schizotypy traits relative to controls; a pattern consistent with that observed in patients with chronic schizophrenia . Together, these findings tentatively suggest that naturally-occurring psychosocial stressors are associated with greater cortisol increases in at-risk individuals compared to healthy controls, whereas the response to experimentally-induced psychosocial stressors is blunted. However, the degree to which HPA axis responses to laboratory-based stressor tasks are relevant to psychosis aetiology is unclear.Unlike studies using experimentally-induced stressor tasks, the lapse of time between stressor exposure and cortisol measurement may be considerable. Whilst elevations in cortisol levels following stressor exposure appear to decrease over time , early life events and trauma exposure are associated with HPA dysregulation later in life, suggesting long term effects of stress exposure . A related issue is that stress measures and cortisol samples may not be collected on the same day, particularly when studies have large assessment batteries spanning several days.
It is possible that day-to-day variations in perceived stress might influence both retrospective reporting of stressful events and cortisol levels, such that greater concordance is observed when measures are collected on the same day. However, to our knowledge, this has yet to be investigated. Determining the extent to which HPA axis responsivity in at-risk youth predicts clinical outcome is important, as such work might ultimately help to identify individuals at increased risk of illness progression by virtue of being more sensitive to the effects of psychosocial stress, enabling targeted interventions. Utilising data from the North American Prodrome Longitudinal Study 2 [NAPLS 2, ] we investigated whether psychosocial stressors, basal cortisol levels, and stressor-cortisol concordance at the baseline assessment differed across healthy controls and CHR subgroups defined on the basis of their clinical presentation at the two-year follow-up . Based on previous studies, we hypothesised that CHR youth who later converted to psychosis would show greater exposure and distress in relation to psychosocial stressors, elevated basal cortisol, and higher stressor-cortisol concordance relative to healthy controls; we also anticipated that CHR non-converters would be intermediate to CHR converters subgroups and healthy controls on these measures. In all analyses we controlled for a range of potential confounders ,cannabis grow system and additionally explored the effect of lapse-of-time between assessments on stressor-cortisol concordance.NAPLS 2 is a consortium of eight research sites examining CHR youth, the aims and recruitment methods for which are detailed elsewhere . Briefly, CHR subjects were help-seeking individuals who met criteria for one or more prodromal syndromes: attenuated psychotic symptoms; brief intermittent psychotic symptoms; or substantial functional decline combined with a first degree relative with a psychotic disorder, or schizotypal personality disorder in individuals younger than 18 years. Prodromal syndromes were assessed using the Criteria of Prodromal Syndromes , based on the Structured Interview for Prodromal Syndromes [SIPS ], conducted by clinically-trained interviewers; psychiatric diagnoses were determined via the Structured Clinical Interview for DSM-IV . CHR individuals who had met criteria for an Axis I psychotic disorder were not eligible for inclusion; treatment with antipsychotic medication was permitted provided that full psychotic symptoms were not present at the time of medication commencement. Healthy controls were recruited from the community and had no personal history or first-degree relative with psychosis and did not meet criteria for any prodromal syndrome. All participants were aged between 12 – 35 years at recruitment. Exclusion criteria for both groups included substance dependence in the past six months, neurological disorder, or full-scale IQ < 70. Non-psychotic psychiatric disorders were permitted in CHR and healthy control groups .Ethical approval was provided by Institutional Review Boards at each NAPLS site , all participants provided informed consent or assent. The current sample includes 662 participants for whom variables of interest at baseline and clinical status at follow-up were available. At baseline, participants provided information on sociodemographic factors and potential confounders, completed stress measures, and collected saliva samples.
Baseline assessments were completed over two or more visits. Where possible, saliva was collected on the same day as daily stressor, life event and childhood trauma measures . However, in some in cases , the baseline assessment was interrupted that lead to a substantial delay in the completion of all measures. In such instances, the remaining baseline measures were collected when the participant was able to return and complete the schedule, with clinical assessments repeated to confirm CHR status. All participants were included in the analysis which accounted for timelapse between assessments. Prodromal symptoms were assessed via the SIPS at 12- and 24-month follow-up assessments and used to categorise CHR subgroups [see Table 1 for details ].Participant date of birth, sex, and ethnicity were assessed via self-report, the latter was subsequently collapsed to a four-level variable . Cannabis use was assessed via a structured interview . For the purposes of the current investigation we created a binary variable indexing current use . Details of all prescribed psychotropic medications were obtained at the baseline assessment via self-report, pharmacy records, and/or medical records. Binary variables were created for current antipsychotic use and current psychotropic use , irrespective of type, dose, or data source.The 58-item, Daily Stress Inventory , was used to determine the presence of minor stressors occurring within the past 24 -hs. Participants indicated whether they experienced each stressor and the level of distress elicited by each endorsed stressor . Total distress scores were then divided by the total exposure score to obtain an average distress per item score . Life events were assessed via the Psychiatric Epidemiology Research Interview Life Events Scale , modified to exclude life events of lesser relevance to youth . The 59 events can be classified as independent or dependent . Interviewers recorded how often each of the 59 events had occurred in the participant’s lifetime and the associated level of distress ; participants could report multiple exposures to the same event , where the maximum occurrence for any single life event in the NAPLS cohort was four. An average life event distress score was derived by dividing the total distress score by the total exposure score . Participants additionally completed the Childhood Trauma and Abuse Scale , a semi-structured interview examining experiences of physical, sexual, and psychological abuse, and emotional neglect, occurring prior to age 16 . Each trauma type was scored as absent/present with a binary variable indexing any form of trauma derived.At the research session, participants provided three saliva samples with a mean salivary cortisol value subsequently derived when two or more samples were available . The median time of collection for the three samples was 1107 h , 1207 h , and 1300 h , respectively. The mean cortisol value, which is highly correlated with area under the curve values , was computed to provide consistency with previous publications . Participants were instructed to avoid consumption of caffeine, alcohol, or dairy products after 1900 h on the day before sampling; individuals who reported non-compliance with these instructions were not excluded as previous analyses performed on a subset of the cohort found no association with these variables and cortisol levels .