It also reduced the separation of the 3 frequency distributions. In addition to the average concentrations, the stronger mechanical air mixing made the transient concentrations become more uniformly distributed in space. Concentration peaks at each distance become much less likely to occur in the outdoor settings than indoors. For example, for both smoking and vaping, less than 1% exceeded 1000 mg/m3 at the 1 m distance outdoors compared to more than 20% indoors. At 2 and 3 m distances, 0% of the 1-second concentrations exceeded 1000 g/m3 outdoors while up to nearly 15% exceeded this level indoors. The separation of the frequency distributions at different distances occurs at a higher cumulative frequency range outdoors -4) than indoors -4). Folding the overhead outdoor umbrella reduced the peak concentrations at each distance; it also reduced the separation of the 3 cumulative frequency distributions versus 4). Like the indoor case versus 4), this could be caused by the stronger air mixing near the source due to a less enclosed environment, making the 1-s PM2.5 concentrations more uniform in space. In this case, all the measured 1- s PM2.5 concentrations dropped below 1000 g/m3 . By obtaining cumulative frequency distributions of short-term concentrations at multiple distances, one can create a graph that shows how the frequency of exceedance varies with distance for a selected peak exposure limit. For example,plant drying rack using the 3 cumulative frequency distributions for outdoor smoking, Figure plotted frequency of exceedance versus distance for 3 selected peak exposure limits .
For each peak exposure limit, the frequency of exceedance decreased with increasing distance from the source. The decreases were more significant for a lower peak exposure limit , allowing the curves for the 3 limits to converge gradually. Assuming the case where <1% of exceedance is needed, keeping 1 m distance from the source could not meet any of the 3 peak exposure limits. Moving from 1 to 2 m distance, we could satisfy the least stringent peak exposure limit . All the 3 peak exposure limits can be met if we moved further to the 3 m distance. The 24-h PM2.5 standard offers a benchmark for assessment of long-term average exposures. The data analysis demonstrated here and provides a possible standardized method to evaluate transient exposures to marijuana aerosols. Optical sensor measurement could drift over time; it is optimal to calibrate optical monitors with the gravimetric shortly before the field experiments. Smoking and exhalation patterns vary across individuals; they could influence the concentration and spatial spread of an emitted plume. For example, Fuoco et al and Zhao et al found particle concentration of e-cigarette vaping increased with puff duration; a higher exhalation velocity could increase the distance impacted by the emission. Future experiments examining how these behavioral patterns affect the proximity effect would be valuable. Particle size distribution influences the deposition of inhaled aerosols. Future research investigating the effect of distance on particle size distribution indoors and outdoors would be useful. This study shows how high PM2.5 levels could be inside a home with a marijuana smoker. PM2.5 has been associated with cardiorespiratory diseases; marijuana-related PM2.5 also has the potential to cause mental disorders.
It is critical to examine the health effects of marijuana secondhand exposure for household members at home . Despite the health risks and societal costs of cigarette smoking, the prevalence of smoking in the USA remains high at ∼19 % . Roughly 44 % of cigarettes are used by smokers with substance abuse/dependence and/or mental illness , and people with almost all substance abuse and mental illness diagnoses have elevated rates of cigarette smoking . Cigarette smokers have elevated rates of both caffeine and marijuana use. Roughly half of smokers drink coffee and report drinking almost twice as much coffee per day as nonsmokers . Similarly, among smokers, 57.9 % have ever used marijuana, and smokers are about 8 times more likely than non-smokers to have a marijuana use disorder , with cigarette smoking and marijuana use being associated even after controlling for potential confounding variables, such as depression, alcohol use, and stressful life events . Given the high comorbidity of smoking and both caffeine and marijuana use, it is important to better understand biological factors that may be associated with these co-occurrences. One of the most well-established effects of chronic cigarette smoking on the human brain is widespread up regulation of α4β2* nicotinic acetylcholine receptors . Recent studies using single-photon emission computed tomography and positron emission tomography have consistently demonstrated significant up regulation of these receptors in smokers compared to nonsmokers. These in vivo studies were an extension of much prior research, including human postmortem brain tissue studies, demonstrating that chronic smokers have increased nAChR density compared to non-smokers and former smokers .
Additionally, many studies of laboratory animals have demonstrated up regulation of markers of nAChR density in response to chronic nicotine administration . In a previous study by our group comparing nAChR availability between smokers and nonsmokers , we explored the effect of many variables, including caffeine and marijuana use. Both heavy caffeine and marijuana use were exclusionary, such that participants drank an average of 1.3 coffee cup equivalents per day and only 12 % of the study sample reported occasional marijuana use. PET results indicated that caffeine and marijuana use had significant relationships with α4β2* nAChR availability in this group with low levels of usage. Based on these preliminary findings, we undertook a study of the effect of heavy caffeine or marijuana usage on α4β2* nAChR density in cigarette smokers.One hundred and one otherwise healthy male adults completed the study and had usable data. Participants were recruited and screened using the same methodology as in our prior reports , with the exception that this study only included Veterans. For smokers, the central inclusion criteria were current nicotine dependence and smoking 10 to 40 cigarettes per day, while for non-smokers, the central inclusion criterion was no cigarette usage within the past year. Heavy caffeine use was defined as the equivalent of ≥3 cups of coffee per day, and heavy marijuana use was defined as ≥4 uses of at least 1 marijuana cigarette per week. Exclusion criteria for all participants were as follows: use of a medication or history of a medical condition that might affect the central nervous system at the time of scanning, any history of mental illness, or any substance abuse/dependence diagnosis within the past year other than caffeine or marijuana diagnoses. Occasional use of alcohol or illicit drugs was not exclusionary. There was no overlap between this study and prior research by our group. During an initial visit,hydroponic rack screening data were obtained to verify participant reports and characterize smoking history. Rating scales obtained were as follows: the Smoker’s Profile Form , Fagerström Test for Nicotine Dependence , Beck Depression Inventory , Hamilton Depression Rating Scale , and Hamilton Anxiety Rating Scale . An exhaled carbon monoxide level was determined using a MicroSmokerlyzer to verify smoking status. A breathalyzer test and urine toxicology screen were obtained at the screening visit to support the participant’s report of no current alcohol abuse or other drug dependencies. This study was approved by the local institutional review board , and participants provided written informed consent.Roughly 1 week after the initial screening session, participants underwent PET scanning following the same general procedure as in our prior reports . Participants from the smoker groups began smoking/ nicotine abstinence two nights prior to each PET session and were monitored as described previously , so that nicotine from smoking would not compete with the radiotracer for receptor binding during PET scanning. Caffeine/marijuana abstinence was initiated 12 h prior to PET scanning, so that acute ingestion/ intoxication would not affect study results. At 11 AM on the scanning day, participants arrived at the VA Greater Los Angeles Healthcare System PET Center, and smoking abstinence was verified by participant report and having an exhaled CO ≤ 4 ppm. Each participant had an intravenous line placed at 11:45 AM in a room adjacent to the PET scanner. At 12 PM, bolus-plus-continuous-infusion of 2-[ 1 8F]fluoro-3-azetidinylmethoxy pyridine was initiated, with 2-FA administered as an intravenous bolus in 5-ml saline over 10 s . Roughly, the same amount of 2-FA was also diluted in 60-ml saline, and 51.1 ml was infused over the next 420 min by a computer-controlled pump .
2- FA-specific activities were similar for the study groups . Groups did not significantly differ for injected or infused doses of 2-FA, or for specific activity . Thus, the amount of 2-FA administered as a bolus was equal to the amount that would be infused over 500 min . This Kbolus was effective for reaching an approximate steady state in recent studies by our group and collaborators . After initiation of the bolus-plus-continuous-infusion, participants remained seated in the room adjacent to the PET scanner for the next 4 h to allow the radiotracer to reach a relatively steady state in the brain. At 4 PM, PET scanning commenced and continued for 3 h, with a 10-min break after 90 min of scanning. Scans were acquired as series of 10-min frames. PET scans were obtained using the Philips Gemini TruFlight , a fully three-dimensional PET-CT scanner, which was operated in non-TOF mode. Reconstruction was done using Fourier rebinning and filtered back projection, and scatter and random corrections were applied. The mean spatial resolution for brain scanning is 5.0 mm by 4.8 mm . 2-FAwas prepared using a published method ; this radiotracer was developed as a ligand specific for β2*-containing nAChRs . A magnetic resonance imaging scan of the brain was obtained for each participant within a week of PET scanning on a 1.5-T Magnetom Symphony System scanner , in order to aid in localization of regions on the PET scans. The MRI had the following specifications: three-dimensional Fourier-transform spoiled-gradient-recalled acquisition with TR = 30 ms, TE = 7 ms, 30 degree angle, 2 acquisitions, 256 × 192 view matrix. The MRI scanning procedure typically lasted ∼30 min. The acquired volume was reconstructed as roughly 90 contiguous 1.5-mm-thick transaxial slices. Blood samples were drawn during PET scanning for determinations of free, unmetabolized 2-FA and nicotine levels in plasma. For 2-FA levels, four samples were drawn as standards prior to 2-FA administration, and nine samples were drawn at predetermined intervals during PET scanning. 2-FA levels were determined using previously published methods . For plasma nicotine levels, blood samples were drawn prior to and following PET scanning. These samples were centrifuged, and venous plasma nicotine concentrations were determined in Dr. Peyton Jacob’s laboratory at UCSF, using a modified version of a published GC-MS method . The lower limit of quantification for this method was 0.2 ng/ ml. In addition to the participants described in this paper, 11 smokers completed study procedures but were excluded from the data analysis because their plasma nicotine levels were unacceptably high . This issue of smokers using nicotine/tobacco during the abstinence period of a brain-imaging study has been reported in prior studies by our group and others , presumably related to difficulty in having tobacco-dependent smokers remain abstinent for a prolonged period.The central study finding was that smokers with concomitant heavy caffeine or marijuana use have higher Vt/fp values in the brainstem and prefrontal cortex than smokers without such use. The study also replicated earlier work demonstrating higher Vt/fp values in the prefrontal cortex and brainstem of smokers than nonsmokers. Taken together, these findings indicate that smokers with concomitant heavy caffeine or marijuana use have greater nAChR up regulation than smokers without concomitant heavy use. The most straightforward and likely explanation for the central study finding is that smokers who use caffeine or marijuana heavily have more nicotine exposure than smokers without such use. This explanation is supported by study data demonstrating that smokers with concomitant heavy caffeine or marijuana use had higher exhaled CO and greater depth of inhalation levels at baseline than smokers without such use . Other data supporting this theory include research demonstrating that caffeine increase nicotine intake in laboratory animals and a study of smokers with heavy marijuana use who had altered lung permeability , which resulted in greater cigarette smoke exposure. Thus, smokers with concomitant heavy caffeine or marijuana use may have increased brain nicotine exposure due to altered smoking topography, effects of caffeine or marijuana on other aspects of nicotine absorption/intake, or both.