Those denial rates were higher than the levels predicted in Hypothesis 1 and occurred despite deniers reporting averages of nine to 11 maximum drinks across probands and offspring. If a clinician had asked these men and women general questions about their drinking status that health care deliverer probably would not have recognized their patient’s drinking problem. The high rate of denial reported here was not anticipated in subjects with higher education and many life achievements, individuals who might have had an advantage in noting that a general alcohol problem was present. However, despite their heavy drinking and multiple alcohol-related problems, their high level of functioning might have convinced these subjects that they did not meet their stereotype of what individuals with AUDs are like. These findings underscore the potential dangers when clinicians rely on simple overall questions to identify individuals who might benefit from motivational interviewing or brief interventions to mitigate future alcohol problems . A more appropriate way to screen patients for alcohol impairment would be to use a standardized and more detailed review of patterns of drinking and alcohol-related problems such as the ten item AUDIT. This instrument takes only a few minutes complete and can be filled out by patients in the waiting room . Such standardized approaches might be especially useful for identifying high functioning individuals with AUDs whose SES might erroneously imply that they are less likely to have alcohol problems. Our analyses searched for potential correlates of one form of denial to help clinicians and researchers better understand denial and to optimize their ability to identify these individuals who might benefit from advice.
The data indicate that false negative self-reports regarding general alcohol problems did not differ significantly across males and females,cannabis grow set up participants who were single or married, levels of education, sex, and in relationship to identification with a religion. Although some prior studies reported a higher rate of denial in African American and Hispanic individuals , that could not be adequately tested in the SDPS sample. It is not surprising that regression analyses in the current data support Hypotheses 2–4, each of which have support in the literature. In both generations, denial was more common among AUD individuals who endorsed fewer DSM-IV criteria, reported lower maximum drinks, and those with alcohol abuse rather than dependence. However, the level of alcohol involvement among these deniers was not benign. Proband and offspring deniers admitted to an average of nine and 11 maximum drinks, respectively, 57 % and 75 % reported drinking higher quantities or for longer periods than intended, 40 % and 23 % admitted to using alcohol in hazardous situations, 13 % and 52 % reported missing important obligations because of alcohol, while 25 % and 22 % endorsed persistent desires or inabilities to cut down or stop drinking. This unhealthy level of drinking and life problems portend a potential for more severe future alcohol problems . Several additional findings in Tables 1 and 3 were not supported in regression analyses where multiple significant characteristics were evaluated together . The specific AUD criteria stated in Hypothesis 5 reflected characteristics of AUD probands whose young adult offspring in a prior paper gave a false negative report of a family history of alcohol problems . Our data indicated a correlation of 0.28 between a proband’s own denial of a general alcohol problem and lack of recognition of problems in that parent by their offspring. Three of the four criteria that were associated with false negative family history reports by offspring also characterized AUD probands with their own denial including much time spent with alcohol , use despite physical/psychological problems , and use despite social/interpersonal problems .
These results highlight AUD criteria clinicians might take time to define when trying to help individuals better understand what AUDs are and to gain greater insight into their future vulnerabilities toward adverse alcohol-related outcomes. The AUD criterion items associated with this form of denial in probands were also evaluated in the 176 AUD offspring. In contrast to probands, deniers in the younger generation evidenced lower proportions who endorsed almost all DSM-IV AUD criteria, including the four items predicted in Hypothesis 5. The only predicted criterion that added significantly to the AUD offspring’s regression equation in Table 4 was giving up important of activities due to alcohol , and this did not contribute significantly to the regression analysis for probands in Table 2. It is not possible to determine whether the difference across the generations regarding specific DSM criteria that related to denial are artifacts of the larger sample of offspring, age differences across the generations, or cohort differences in the cultures in which they live. However, it is important to emphasize that regression analyses in both generations indicated that denial was related to a lower degree of both alcohol and drug use and problems. Regarding the latter, adverse consequences related to other drugs might increase a person’s awareness of potential problems with alcohol. Another interesting finding related to the overall differences across generations regarding the specific criteria items endorsed by AUD probands and AUD offspring in the first data columns of Tables 1 and 3. One striking finding involved the 4% of AUD probands overall who admitted to tolerance in the prior five years compared to 57 % who endorsed tolerance in AUD offspring. A cursory review of tolerance reports over the years in SDPS AUD probands indicated that this variable had been endorsed by AUD probands at age 35 at a rate similar to the current AUD offspring. However, the proportions of probands who reported tolerance in the five years prior to interview decreased steadily with each subsequent interview.
The key aspect of the tolerance question used here might be the emphasis on the recent five-year period. It is possible that self-perceived tolerance might be strongest at younger ages when drinking is escalating but might not be as apparent as individuals maintain and decrease the maximum drinks with advancing age. Space constraints do not allow for an expanded examination of the phenomenon of changes in rates of endorsement of AUD criteria as individuals age, but that question will be revisited in a future paper. The data presented here must be viewed with several caveats in mind. First, we report detailed information gathered prospectively every five years from 453 families by the same principal investigators using the same interviews and questionnaires across two generations. Those steps allowed a unique opportunity to ask questions and compare results across time and across generations. However, it would be difficult and costly to carry out a similar approach in a much larger and more diverse population, with the result that it is unclear whether the current findings would be seen in families with different racial or ethnic backgrounds, a wider range of socioeconomic characteristics, and individuals from different areas of the world. Second, denial is a broad concept lacking general agreement regarding the optimal definition, and the current analyses focus on only one of several types of denial that relate to substance use and problems. Third, the global question of how individuals view their drinking pattern was developed for this study and has not been formally evaluated for reliability and validity. Finally, to keep the time spent by participants every five years to a reasonable limit the characteristics evaluated here were not exhaustive and there is a need for future studies to consider a wider range of intrapersonal and societal mechanisms that might have contributed to the type of denial studied here. In conclusion,grow rack systems denial of a general alcohol problem by individuals who admitted to multiple AUD criteria items was quite common in the SDPS, despite prodigious maximum drinking quantities. This pattern of denial indicates that greater efforts need to be made to educate our patients and our colleagues regarding what an AUD is and how serious the prognosis can be. For AUD probands, deniers were less likely to endorse several specific criteria that might offer some insights into why they do not consider themselves problem drinkers. Whether these problems were truly absent or if the person was reluctant to admit their presence, motivational interviewing, brief interventions and related approaches might help patients recognize that the absence of endorsement of those four items does not mean that the alcohol problems are not serious.Soon after the British physician W. B. O’Shaugnessy had brought back from India an account of the remarkable effects of the cannabis plant, the medical communities in Europe and the US eagerly adopted it into their pharmacopeias. Cannabis, noted Robert Christison in his 1848 dispensatory, “promises to be an important article in Materia Medica…which deserves a more extensive enquiry than any hitherto instituted.” Those propitious times would soon end, however, as a collective mood swing pushed cannabis and its medicinal properties into a limbo of scientific indifference.
And there it stayed for several decades—despite the lonely sounding of a few ‘voices crying in the wilderness’— until about 10 years ago, when the serendipitous discovery of a brain receptor that binds cannabis-like compounds brought it back into the limelight. The molecular cloning of the first cannabinoid receptor was quickly followed by the identification of a second sub-type in the immune system and then by the characterization of two endogenous cannabis-like compounds with their attendant pathways of biosynthesis and inactivation. These discoveries eventually led to the chemical syntheses of potent ligands selective for either receptor sub-type, which have provided invaluable clues to help explain how the endogenous cannabinoid system may influence physiological functions as diverse as pain, movement control and blood pressure. At the same time, these tools have rejuvenated Christinson’s plea for “a more extensive enquiry” into the medicinal potential of cannabinoids, allowing researchers to test popular notions such as their appetite-stimulating or pain-killing effects, as well as to explore newer avenues of research. In this issue of Nature Medicine, a paper by Galve-Roperh et al. provides an excellent example of the cannabinoids’ therapeutic potential. Galve-Roperh et al. report findings that indicate a new cannabinoid-based approach for the treatment of malignant gliomas. Malignant gliomas are a relatively uncommon but uniformly fatal form of brain tumor that can be modeled in rodents by inoculating glioma cells into the brain parenchyma. The resulting tumor grows very rapidly, leading to the animal’s death within 2–3 weeks after the initial cell inoculation. Galve-Roperh et al. found that administration of cannabinoid agonists into the tumor by means of an osmotic pump connected to an intracerebral cannula eradicated the tumor in one-third of the inoculated animals, and prolonged the survival of another one-third for up to 6 weeks. In the remaining group of animals, the cancer was insensitive to the cannabinoids and continued its malignant course unhindered. Although incomplete, these findings must be seriously considered, as glial tumors are peculiarly resistant to traditional therapy. To identify which receptors are involved in the anti-cancer actions of the cannabinoids, Galve-Roperh et al. turned to a cell culture system. Based on their earlier observation that C6 glioma cells undergo programmed death after exposure to a cannabinoid drug, they characterized this effect pharmacologically. Unexpectedly, they discovered that both CB1 and CB2 receptors are involved: CB1 and CB2 antagonists were able to prevent cannabinoid-induced cell death only if they were added together to the glioma cultures. This finding indicates that each cannabinoid receptor can trigger a full-fledged apoptotic response independently of the other, as long as it is free to interact with an agonist. Does this also occur in vivo? An affirmative answer to this question, which Galve-Roperh et al. did not address in their study, might be of considerable therapeutic importance. It would indicate that selective CB2 receptor agonists can arrest the progression of malignant gliomas without exerting the psychotropic and hypotensive effects that accompany the recruitment of central and peripheral CB1 receptors. As with many other Gi/Go-proteinlinked receptors, agonist binding of CB1 and CB2 receptors causes inhibition of adenyl cyclase activity and stimulation of mitogen-activated protein kinase activity. However, the results reported by Galve-Roperh et al. do not support the idea of direct involvement of these signaling pathways in the apoptotic actions of the cannabinoids. Rather, they indicate that cannabinoid-mediated glioma cell death may be signaled through accumulation of the lipid second messenger, ceramide, followed by activation of the extracellular signal-regulated kinase cascade . Ceramide production is a ubiquitous cellular response triggered by cytokines, hormones and other intercellular mediators.