Is there a relationship between abuse of alcohol and illicit drugs seen in hair results?
Pragst et al.
Institute of Legal Medicine University Medicine Charité Berlin Germany
* CorrespondenceFritz Pragst, Institute of Legal Medicine, University Medicine Charité, Turmstraße 21, Haus N, 10559 Berlin, Germany.
Email: fritz.pragst@charite.de
Abstract
Combined use of alcohol and illicit drugs is a serious health and social problem. In this study, it was examined, whether a relationship between alcohol and drug abuse can be ascertained by comparison of alcohol marker and drug concentrations in hair. In the frame of a social support system for families with parental abuse of illicit drugs, hair samples were analyzed between 2011 and 2022 for methadone, heroin (6‐acetylmorphine), cocaine, amphetamine, ecstasy (MDMA), cannabinoids (THC), and the alcohol markers ethyl glucuronide (EtG) and ethyl palmitate (EtPa). For 1314 hair samples from adolescent and adult family members, the hair results show a prevalence of combined occasional or regular drug use and social or abusive alcohol use of 41%–60% except heroin (35%). The drug concentrations were statistically compared in the three categories of abstinence or moderate drinking, social drinking, and alcohol abuse. For the most frequently detected drug cocaine (n = 703), a significant increase of the concentrations with rising alcohol consumption was found. The frequent detection of cocaethylene proved the preferred simultaneous intake of both substances. For THC (n = 489), no significant difference between the alcohol consumer groups was seen. Concerning the less frequently detected methadone (n = 89), 6‐acetylmorphine (n = 92), amphetamine (n = 123), and MDMA (n = 105), no clear trend between drug and alcohol marker results was determined. It is concluded that the evaluation of hair results is an appropriate way to study the extent of combined drug–alcohol consumption and complements other studies based on acquisition of consumption data by interview or questionnaire.
Article notes
Pragst F , Niebel A , Thurmann D , et al. Is there a relationship between abuse of alcohol and illicit drugs seen in hair results? Drug Test Anal. 2025;17(2):259‐271. doi:10.1002/dta.3702 38686500 PMC11842179
1INTRODUCTION
Polysubstance use, which means the simultaneous (at the same time) or sequential (on separate occasions) intake of more than one substance over a given period, is very common among drug consumers. 1 , 2 , 3 , 4 Reasons are to enhance or to prolong the pleasurable effects or to alleviate the symptoms of withdrawal. In this context, alcohol in combination with illicit drugs plays a predominant role as it was reported for heroin, 5 , 6 cocaine, 3 , 7 , 8 , 9 , 10 amphetamine, 11 methamphetamine, 12 , 13 ecstasy, 14 and cannabinoids. 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 According to the current literature about polysubstance use, 22 the term “combined use” or “co‐use” is an umbrella term, whereas “concurrent use” means use of each substance on separate occasions, often as a substitute for the other substance, and “simultaneous use” means use of the substances at the same occasion with overlapping effects, mainly to increase benefits or to reduce negative effects of the single drugs. Of course, routine hair analysis does not distinguish between concurrent and simultaneous use except for cocaine which forms the mutual metabolite cocaethylene in case of simultaneous consumption with alcohol.
Information about prevalence, motivations, and effects of polysubstance use were mainly obtained by questionnaires. Hair analysis for its detection was mainly limited to illicit drugs and included alcohol markers only in two studies. 26 , 27
In a social support system for families with small children and known or suspected abuse of illicit drugs of the parents, hair samples were regularly analyzed between 2011 and 2022 for methadone, heroin, cocaine, amphetamine, ecstasy, and cannabinoids. 28 , 29 , 30 In most cases, also the alcohol markers ethyl glucuronide (EtG) and ethyl palmitate (EtPa) were determined. 31 In the present study, it was examined whether a relationship between use of illicit drugs and alcohol of the adults and adolescents can be seen from the hair results.
2MATERIAL AND METHODS
2.1Project, tested individuals and hair samples
This study was performed in the frame of a social support system for families with known or suspected parental abuse of illicit drugs in the Hanseatic City of Bremen in Germany. Hair analysis for drugs and alcohol markers was used as the essential diagnostic tool. Between 2011 and 2022, altogether, more than 3800 hair samples from parents and children were analyzed. More details about the whole project were described in previous papers. 28 , 29 , 30 , 31 The present study includes 1314 hair samples from adult and adolescent family members, which were analyzed for both drug and alcohol markers. The age ranged from 15 to 70 years (mean 32.7 years, median 33 years). There were 518 male (39.4%) and 777 female (59.2%) persons tested. For the remaining 19 persons (1.4%), the gender was not reported.
The hair samples were collected by trained personnel of the local health authority of Bremen from the vertex posterior region using the hair collection kit of the Institute of Legal Medicine of the University Hospital Charité Berlin by cutting as close as possible above the skin. Kind, frequency, and last application of hair cosmetics as well as the length of uncolored proximal hair were recorded in the sampling protocol.
2.2Methods and interpretation
The testing for drugs in hair was performed by a validated LC–MS/MS method with lower limits of quantification (LOQs) of 3–10 pg/mg for all drugs and metabolites. The methods used for sample preparation and measurements as well as the validation were described in detail in previous papers. 29 , 30 Briefly, the hair was decontaminated by washing in water and two times in acetone. After drying, it was cut to 1–2 mm pieces and 20–30 mg were incubated for 18 h with 0.5 mL of a mixture of methanol/acetonitrile/2 mM of ammonium formate (25:25:50, v/v/v) and a mixture of 43 deuterated standards (each 5 ng) under gentle shaking at 37°C. Then, the mixture was centrifuged, the supernatant separated, and the incubation of the hair pieces was repeated for 18 h with another 0.5 mL of the solvent mixture. Both extracts were united and evaporated in a nitrogen stream to a residue of 0.5 mL to remove most of the organic solvents. Five microliters of the residue were injected for analysis without further cleanup procedures.
The analyzed hair segment was 0–6 cm or full length in case of shorter hair. The drug results were interpreted in the four categories: negative, low concentration, occasional use, and regular use with the following concentration ranges for low, occasional, and regular (ng/mg): heroin (6‐acetylmorphine) <0.1; 0.1 to <2.0; ≥2.0, cocaine <0.5; 0.5 to <4.0; ≥4.0, amphetamine <0.1; 0.1 to <2.0; ≥2.0, ecstasy (MDMA) <0.1; 0.1 to <2.0; ≥2.0, and THC <0.05; 0.05 to <0.7; ≥0.7. For methadone, which was applied in opiate maintenance treatment to many of the subjects, only the ranges <2.0 ng/mg (low) and ≥2.0 ng/mg (regular) were used for interpretation.
The determination of the alcohol markers occurred by LC–MS/MS for EtG (LOQ 1.35 pg/mg) and by headspace solid‐phase microextraction and GC–MS for EtPa (LOQ 19 pg/mg). A detailed description of the methods and of the validation was given in a previous paper. 31 The tested hair segment was 0–3 cm or full hair length in case of shorter hair. For measurement of EtG, the hair was washed with dichloromethane (30 min) and methanol (1 min), and 25 mg of the dried proximal 3‐cm‐long hair segment or of the whole length in case of shorter hair was cut in small pieces, ground by a ball mill and incubated with 500‐μL water plus 10‐ng EtG‐d5 in 5‐μL acetonitrile/water (9:1 v/v) for 24 h. The extract was separated by a syringe equipped with a 0.2‐μm PTFE microfilter, and 10 μL was directly injected for LC–MS/MS measurement.
For determination of EtPa, 20‐mg hair was cut into small pieces, washed two times for 10 min with n‐heptane, and extracted with a mixture of 0.5 mL of dimethylsulfoxide (DMSO) and 2 mL of n‐heptane plus 20‐ng EtPa‐d5 for 20 h at room temperature. After cooling at 0°C, the heptane layer was separated by decantation and evaporated, and the residue was submitted to automated HS‐SPME‐MS from 1‐mL phosphate buffer pH 7.6 plus 0.5‐g NaCl.
The combined interpretation of both markers concerning alcohol consumption was based on the cut‐offs of the 2019 consensus of the Society of Hair Testing on alcohol markers in hair (5 and 30 pg/mg for EtG and 0.12 and 0.35 ng/mg for EtPa) 32 and led to a classification of the results into the three categories: abstinence or moderate drinking, social drinking, and alcohol abuse. Hair cosmetics as reported by the tested person, obvious from the appearance of the sample or from the color of the hair extracts, was considered in the interpretation of both drugs and alcohol markers.
2.3Statistical evaluation
For statistical comparison of the drug concentration between the alcohol consumer groups by the Kruskal–Wallis test and the Mann–Whitney U‐test, the software IBM SPSS, Version 28, was used. The significance level p < 0.05 was taken as the criterion for difference.
3RESULTS AND DISCUSSION
3.1Frequency of positive drug and alcohol results
The hair testing results for drugs and alcohol markers of the 1314 samples are shown in Table 1. In the present study, methadone, heroin, cocaine, amphetamine, MDMA, and THC were included. None of these drugs were detected in 396 samples (30.1%), whereas in the remaining 918 samples (69.1%), at least one, but mainly several drugs were found. Cocaine was the most frequently detected drug with 703 positive samples (53.5%) followed by THC with 489 samples (37.1%). The frequency of methadone with 89 samples (6.8%), heroin with 92 samples (7.0%), amphetamine with 123 samples (9.4%), and MDMA with 105 samples (8.0%) was much lower. Methamphetamine was not detected in this North German population.
| Drug (range, ng/mg) | Interpretation ranges a , ng/mg | Alcohol marker results Number of samples and percentage (%) | |||
|---|---|---|---|---|---|
| Abstinence or mode‐rate drinker (N = 765) | Social drinker (N = 306) | Alcohol abuse (N = 243) | Total positive | ||
| All drugs negative | ‐‐‐‐‐ | 255 (19.4) | 71 (5.4) | 70 (5.3) | 396 (30.1) |
| One or more drugs b | Low concentr. | 178 (13.5) | 84 (6.4) | 54 (4.1) | 316 (24.0) |
| Occasional use | 197 (15.0) | 83 (6.3) | 51 (3.9) | 331 (25.2) | |
| Regular use | 135 (10.3) | 68 (5.2) | 68 (5.2) | 271 (20.6) | |
| Total | 510 (38.8) | 235 (17.9) | 173 (13.2) | 918 (69.9) | |
| Methadone c | Negative | 712 (54.2) | 288 (21.9) | 225 (17.1) | |
| (0.01–47.6) | <2 | 23 (1.8) | 8 (0.61) | 4 (0.30) | 89 (6.8) |
| ≥2 | 30 (2.3) | 10 (0.76) | 14 (1.06) | ||
| Heroin (6‐AM) | Negative | 711 (54.1) | 290 (22.1) | 221 (16.8) | |
| (0.01–11.2) | <0.1 | 19 (1.4) | 7 (0.53) | 12 (0.91) | 92 (7.0) |
| 0.1 to <2.0 | 27 (2.1) | 6 (0.46) | 8 (0.61) | ||
| ≥2 | 8 (0.61) | 3 (0.23) | 2 (0.15) | ||
| Cocaine | Negative | 399 (30.4) | 119 (9.1) | 93 (7.1) | |
| (0.01–105) | <0.5 | 245 (18.6) | 108 (8.3) | 77 (5.8) | 703 (53.5) |
| 0.5 to <4.0 | 75 (5.7) | 34 (2.6) | 27 (2.1) | ||
| ≥4 | 46 (3.5) | 45 (3.4) | 46 (3.5) | ||
| Amphetamine | Negative | 706 (53.7) | 268 (20.4) | 217 (16.5) | |
| (0.01–20.1) | <0.1 | 30 (2.3) | 20 (1.5) | 14 (1.07) | 123 (9.4) |
| 0.1 to <2.0 | 23 (1.8) | 13 (0.99) | 10 (0.76) | ||
| ≥2 | 6 (0.46) | 5 (0.38) | 2 (0.15) | ||
| MDMA | Negative | 715 (54.4) | 276 (21.0) | 218 (16.6) | |
| (0.01–11.5) | <0.1 | 27 (2.1) | 8 (0.61) | 11 (0.83) | 105 (8.0) |
| 0.1 to <2.0 | 18 (1.4) | 16 (1.1) | 10 (7.6) | ||
| ≥2 | 5 (0.38) | 6 (0.53) | 4 (0.30) | ||
| THC | Negative | 476 (36.2) | 187 (14.2) | 163 (12.4) | |
| (0.01–19.5) | <0.05 | 73 (5.6) | 27 (2.1) | 20 (1.5) | 489 (37.1) |
| 0.05 to <0.7 | 156 (11.9) | 65 (4.9) | 44 (3.3) | ||
| ≥0.7 | 60 (4.6) | 27 (2.1) | 16 (1.3) | ||
For interpretation, the results were arranged for each drug according to their concentrations in four categories: “Negative,” “Low concentration,” “Occasional use,” and “Regular use.” The corresponding interpretative concentration ranges are given in Section 2.2 and in the second column of Table 1 and were equally used in the forensic expertise of these cases.
In regard of the alcohol markers, the interpretation was based on the first line on EtG in the three categories “Abstinence or moderate drinking” (EtG <5 pg/mg), “Social drinking” (EtG ≥5 to <30 pg/mg), and “Alcohol abuse” (≥30 pg/mg). EtPa was used as a confirmatory parameter with the corresponding cut‐offs of 0.12 and 0.35 ng/mg and was particularly considered in cases of recent aggressive hair cosmetics and negative EtG results. Generally, hair cosmetics was recorded during hair sampling and was taken into account in each case. In the same way as for drugs, the interpretation of the alcohol markers given in the forensic expertise of the cases was used for the present evaluation. From the 1314 samples, the number in the category abstinence or moderate drinking (765 samples, 58.2%) was clearly higher than that of social drinking (306 samples, 23.3%) and alcohol abuse (243 samples, 18.5%). This higher occurrence of abstinence or moderate drinking is also separately valid for each of the four categories of drug use.
The comparison of drug and alcohol markers is limited by the different hair lengths used for the determination of drugs (0–6 cm or total length, if shorter) and alcohol markers (0–3 cm or total length, if shorter). All hair tests were performed in forensic routine work, and the shorter hair segment for the alcohol marker is caused by their limited stability in hair and the definition of the cut‐offs for 0–3 cm, 32 whereas in case of the drugs, the segment 0–6 cm was routinely analyzed in order to control a longer time period. The different time period of about 6 months before sampling for drugs and only about 3 months before sampling for alcohol markers can have essentially affected the studied relationship if in the last 6 months, before collection of the hair sample, a drastic change in the consumption habits of drugs occurred. It follows from segmental hair analysis in previous studies, 33 , 34 that this is not relevant for the majority of the cases but may have contributed to the large variation seen in the statistical comparison.
The number of results with occasional or regular drug use in total and with combined social or abusive alcohol consumption is shown for all drugs in Table 2. The portion of combined use with alcohol was lowest for heroin with 35.2% and highest for MDMA with 61.0%. That means, between 35% and 61% of the occasional or regular drug users have also a social or abusive alcohol consumption.
| Drug (ng/mg) | Number of results for occasional or regular drug use | Combined drug–alcohol use, % | |
|---|---|---|---|
| Total | With social or abusive alcohol | ||
| Methadone a (≥2) | 54 | 24 | 44.4 |
| Heroin (6‐AM ≥0.1) | 54 | 19 | 35.2 |
| Cocaine (≥0.5) | 273 | 152 | 55.7 |
| Amphetamine (≥0.1) | 59 | 30 | 50.8 |
| MDMA (≥0.1) | 59 | 36 | 61.0 |
| THC (≥0.05) | 368 | 152 | 41.3 |
It is of general interest whether occasional or regular drug consumers drink more or even less alcohol than drug‐abstinent persons. In order to examine this question, two approaches were chosen: (I) The statistical comparison of the drug concentrations between the three alcohol consumer categories and (II) the evaluation of the frequency of samples with the possible combinations between the three alcohol consumer groups and the four drug use groups.
3.2Relationship between drug concentrations and alcohol consumption
The statistical comparison of the drug concentrations between the three alcohol consumer groups was performed by the software IBM SPSS. The complete statistical data for all six drugs are given in Table S1. The concentrations were generally not normally distributed with the most values at low concentrations and many outliers of high concentrations as it was obvious from the positive kurtosis (+2.2 to +59.8) and skewness (+0.6 to +7.1). This strongly positive skewed and peaked deviation from the normal distribution is also seen from the box–whiskers plots of the THC and cocaine concentrations for the three alcohol consumer groups in Figures 1 and 2.
Because of this missing normal distribution, the nonparametric Kruskal–Wallis test and Mann–Whitney U‐test were chosen for comparison of all three groups and for pairwise comparison with the significance level of p < 0.05. Except for cocaine, for none of the remaining drugs, a significant difference between the three alcohol consumer groups was found. This is shown for THC in Figure 1. The relatively small differences between the mean values (0.77, 0.54, and 0.61 ng/mg) and the medians (0.16, 0.14, and 0.16 ng/mg) are irrelevant considering the strong variation of the concentrations within the groups. Accordingly, the significance was clearly above 0.05 with p = 0.960 for the Kruskal–Wallis test and pairwise p = 0.803, 0.843, and 0.946 between the three groups by the Mann–Whitney U‐test.
The validity of the statistical test results is generally limited by the fact that in addition to the tested drug, in a high percentage of samples, further drugs were detected with a possibly different effect on the alcohol consumption (Table S1). Therefore, from the altogether 489 THC‐positive samples, the 129 exclusively THC‐positive samples (86 abstinence + moderate drinking, 28 social drinking, and 15 alcohol abuse) were separately examined. This led to a slight decrease of the p‐values with p = 0.555 for the Kruskal–Wallis test and p = 0.759, 0.270, and 0.516 between the three groups by the Mann–Whitney U‐test, but there was again no evidence of significant differences between the alcohol consumption groups.
This is similar for methadone, heroin (6‐AM), amphetamine, and MDMA. The much lower number of positive samples of these drugs additionally impeded the statistical evaluation and did not allow the separate evaluation of the still rarer single‐drug samples (Tables 1 and S1).
A significant difference between the three alcohol consumer groups was found for cocaine as shown by the box–whiskers plots in Figure 2. With increasing alcohol consumption, the mean, as well as the median cocaine concentration, clearly rises, the mean from 2.67 through 4.22 to 5.00 ng/mg and the median from 0.17 through 0.24 to 0.42 ng/mg. The Kruskal–Wallis test showed with p < 0.001 a significant difference between the groups, whereas the Mann–Whitney U‐test distinguished clearly the abstinence + moderate drinking group from the social drinking group (p = 0.022), as well as from the alcohol consumption group (p < 0.001). However, there was a marginally increased significance of p = 0.057 between the social drinking group and the alcohol consumption group.
This result suggests that, as a mean, persons with alcohol abuse tend more to cocaine use than alcohol‐abstinent or moderate‐drinking persons. In order to exclude an influence of additionally taken other drugs, from the total of 703 cocaine‐positive samples, the 283 samples with cocaine as the only positive drug (139 abstinence + moderate drinking, 84 social drinking, and 60 alcohol abuse) were separately evaluated. Unexpectedly, the discrimination between the three alcohol consumer groups was diminished in comparison with the total of cocaine‐positive samples with mean concentrations of 2.44, 3.22, and 3.82 ng/mg; median concentrations of 0.12, 0.15, and 0.25 ng/mg; and significance values p > 0.05 of the Kruskal–Wallis test (0.207) and of the Mann–Whitney U‐test (0.277, 0.090, and 0.545). Only the comparison between abstinence + social drinking and alcohol abuse (p = 0.090) was relatively close to 0.05.
3.3Relative frequencies of samples with the possible combinations of alcohol consumer groups and drug use groups
The numbers of samples belonging to the 12 combinations of the three alcohol consumption groups (abstinence + moderate social drinking, social drinking, and alcohol abuse) and the four drug consumption categories (negative, low, occasional, and regular) are given in Table 1 for all drugs. For a comprehensive comparison, relative frequencies are more suitable than the absolute numbers. Therefore, for each of the four drug consumption categories, the percentage of the three alcohol groups was calculated. The resulting relative frequencies are shown for THC in Figure 3 and for cocaine in Figure 4. Only for these two drugs, the number of samples in all 12 combinations was sufficient for a statistical comparison. For methadone, heroin, amphetamine, and MDMA, the numbers were insufficient since only two to four samples were allocated to some combinations.
For THC, no clear trend between the cannabis consumer groups is seen (abstinence or moderate drinking, 57.6% to 60.8%; social drinking, 22.6% to 26.2%; and alcohol abuse, 15.5% to 19.7%). However, for cocaine, the percentage of alcohol abuse cases increases with the cocaine concentration from 15.2% (cocaine negative) through 17.9% (cocaine, <0.5 ng/mg) and 18.4% (cocaine, 0.5 to <4.0 ng/mg) to 36.5% (cocaine, ≥4.0 ng/mg). On the contrary, the percentage of abstinence or moderate alcohol use cases decreases in the same order from 65.2% to 57.0% and 51.0% to 38.3%. For social drinkers, the trend resembles more alcohol abuse than abstinence + social drinking.
These findings confirm the results of the Kruskal–Wallis test and the Mann–Whitney U‐test in Section 3.2.
3.4Cocaethylene (CE)
Different from the other drugs, simultaneous use of cocaine (COC) and alcohol can be distinguished from concurrent use by the common metabolite cocaethylene (CE) in hair. 35 , 36 On the other hand, CE can also occur as a component in illicit cocaine, if ethanol is used for the purification of crude cocaine base. 37 , 38 This can lead to a wrong interpretation of simultaneous cocaine and alcohol use. However, it can be concluded from the absence of CE (<LOD ≈ 0.01 ng/ng) in 80 samples with cocaine concentrations of 0.5–76.7 ng/mg (see below) that its origin as a component of illicit cocaine is improbable in this study and that it exclusively occurs as a cocaine metabolite.
The forensic profile of CE was reviewed by Jones. 39 It is known that the metabolic re‐esterification of cocaine to CE in the presence of ethanol is catalyzed by the same nonspecific hepatic cocaine carboxylesterase that hydrolyzes cocaine into benzoylecgonine. 40 That means, benzoylecgonine (BE) and CE are products of competing metabolic reactions. Therefore, besides the concentration of CE, the concentration ratios CE/COC and CE/BE are characteristic of the extent of simultaneous use with alcohol.
It follows from pharmacokinetic studies that, after oral intake of 1 mg/kg alcohol and subsequent snorting of cocaine, the area under the plasma concentration versus time curve (AUC) of CE was about 20% of that of COC. 41 In studies with deuterium‐labeled cocaine and the same alcohol dose, 24 ± 11% of intravenous, 34 ± 20% of oral, and 18 ± 11% of smoked cocaine were converted to CE. 42 , 43 From the viewpoint of hair analysis, it is an important result of these kinetic studies that the ratio CE/COC is essentially determined by the blood alcohol concentration during cocaine use and only to a much lower extent by the cocaine dose and the consumption frequency. With the assumption of a similar incorporation rate of CE and COC, this should also be valid for hair. It was concluded from literature data reviewed in a previous paper that CE/COC ratios >0.10 in hair indicate regular use of the drug in combination with high alcohol levels. 35
In the present study, only hair samples with a COC concentration of ≥0.5 ng/mg corresponding to occasional or regular use were evaluated concerning CE in order to exclude false negative CE results at lower COC concentrations. At COC = 0.5 ng/mg, and with LOQ of CE of 0.01 ng/mg, CE could be determined down to a CE/COC ratio of 0.02. Furthermore, possible low false positive COC results due to external contamination were minimized by this cut‐off.
From the 267 hair samples with COC of ≥0.5 ng/mg, CE was detected in 186 samples (69.7%). That means that more than two‐thirds of the occasional or regular cocaine users consume the drug simultaneously with alcohol. Between the alcohol consumer groups, the portion of CE‐positive results increased from abstinence + moderate drinking (57 from 118 samples, 48.3%) to social drinking (63 from 69 samples, 83.5%) and alcohol abuse (67 from 73 samples, 91.3%). In the same order, an increase of the ratios CE/COC and CE/BE was found as shown in Figure 5. The detailed statistical data of the CE‐positive and the CE‐negative samples are given in Tables S2 and S3.
As expected, the increasing portion of CE‐positive samples and of the CE/COC and CE/BE ratios in the three groups confirm, as a mean, the increasing alcohol consumption as shown by the markers EtG and EtPa. However, there is a large variation within the groups. For example, in the group of alcohol abstainers and moderate drinkers, there are six cases with CE/COC ratios ≥0.3 at COC concentrations of 0.50–3.36 ng/mg, which can be interpreted as occasional cocaine use always under high alcohol level. On the other hand, in the group of alcohol abuse, there are six cases with CE/COC ≤0.02 at COC concentrations of 4.39–31.8 ng/mg for which the use of alcohol and cocaine should have occurred mainly on different occasions.
There were 80 cases with COC ≥0.5 ng/mg without detection of CE. The COC concentrations of these cases (mean 4.7 ng/mg, median 1.3 ng/mg) were significantly lower than those of the 186 CE‐positive samples (mean 11.1 ng/mg, median 5.5 ng/mg). Together with the increase of the portion of CE‐positive cases and of the CE/COC and CE/BE ratios at rising alcohol consumption in the three alcohol consumer groups, this result supports the conclusion of Sections 3.2 and 3.3 about the positive relationship between cocaine and alcohol use. It follows furthermore from the high prevalence of CE that the co‐use of both substances described that there is predominantly a simultaneous consumption.
3.5Literature review of cannabis and cocaine co‐use with alcohol and comparison with results of the present study
3.5.1Relationship between use of alcohol and cannabis
The discussion of the results in the context of literature data about previous studies shall be limited to THC and cocaine for which the larger number of positive samples allows a conclusive interpretation. There are numerous papers about the co‐use of cannabis and alcohol, which were comprehensively reviewed by Subbaraman, 15 Risso et al., 16 Lee et al., 17 Yurasek, 24 and Gunn et al. 25 The studies were based mainly on self‐reports and questionnaire surveys gathered by in‐person sessions with therapists or online by computer or smartphone with up to five reports per day over several weeks. Included were patients with alcohol and/or cannabis use disorder, consumers of medical cannabis, as well as recreationally cannabis‐consuming adolescents, returning combat veterans, and college students. There were also placebo‐controlled laboratory studies with defined alcohol and THC doses accompanied by breath alcohol tests and blood and urine tests for cannabinoids in which cannabis has been shown to enhance the pleasurable effects of alcohol and to increase blood alcohol levels at various doses. 23 , 44 , 45
These studies provided evidence for both substitution and complementary effects of alcohol–cannabis co‐use. However, the ratio of substitution versus complementary effects depends on patterns and context of co‐use, timing and order of use, cannabinoid formulation, pharmacokinetic interactions, and user characteristics.
Cannabis and alcohol acting as substitutes was described in patients of either alcohol use disorder or cannabis use disorder with decreased doses in co‐use as compared with the use of alcohol or cannabis alone. 46 , 47 Consumers of medical cannabis endorsed the use of cannabis as a substitute for alcohol. 48 A substitute relationship was also assumed for students who used alcohol or cannabis to cope with stressful events, the more they drank on a given evening, the less likely they were to use cannabis. 49 Altogether, co‐use of cannabis and alcohol as substitutes occurs preferentially concurrently (not at the same events, no overlapping effects) and results in lower doses in comparison with both substances alone.
In contrast, the complementary consumption of both substances occurs simultaneously. Motivations are conformity (e.g., “to fit in with a group”), to enhance positive psychoactive effects (“to get a better high”), calm and coping (“to calm me down” or “to cope with anxiety”), and social (“because it is customary on special occasions,” “as a way to celebrate”). 50 In individuals diagnosed with both alcohol and cannabis use disorder or alcohol use disorder alone, daily cannabis use was associated with more alcohol consumption than on cannabis‐free days. 51 In a large, general population sample, simultaneous use was associated with both increased frequency of cannabis and alcohol use and increased quantity of alcohol use. 52
From physiological point of view, the endocannabinoid system regulates both cannabis and alcohol reinforcement. 53 It has been shown that cannabinoid receptor agonists stimulate the motivational aspects of alcohol, including its consumption and self‐administration. Chronic alcohol consumption leads to the downregulation of the cannabinoid receptor CB1 and in this way to a cross‐tolerance between alcohol and exogenous as well as endogenous cannabinoids. This can lead to increased dose of both substances independent of substitutional or complementary use.
The relationships of cannabis policy liberalization and alcohol use and co‐use with cannabis were reviewed by Guttmannova et al. 18 and Pacula et al. 19 The proportion between the consumption of cannabis and alcohol in a population is influenced, among others, by the general availability of both substances including pricing. Both reviews came to the conclusion that there remains insufficient evidence—both in terms of quantity and quality—to conclude that cannabis policy liberalization in US states is associated with either increases or decreases in alcohol use or alcohol‐related outcomes. For instance, the monthly purchased pure ethanol amount in the states of Colorado, Oregon, and Washington, where recreational cannabis was legalized, was compared with states that had not legalized recreational cannabis. 21 The results were inconsistent, with an average monthly decrease in Colorado and Oregon and an increase in Washington.
In summary, it follows from the comprehensive literature that co‐use of alcohol is very common among cannabis users (>75%) 19 but that, in view of the various influencing factors and of the widely differing results of the studies, no general statement is possible about an enhancement or reduction of alcohol consumption by cannabis.
Until now, hair analysis was not described in this context. However, the evaluation of the concentrations of THC and alcohol markers in hair in the present study essentially confirms the previous knowledge summarized above. One hundred ninety‐nine of the 489 THC‐positive samples (40.7%) showed EtG results in the range of social or abusive drinking. It can be assumed that the real percentage is still higher since also a part of the moderate drinkers with EtG < 5 pg/mg can be expected to co‐use cannabis. Neither from the comparison of the THC concentrations between the three alcohol consumer groups (Section 3.2 and Figure 1) nor from the sample frequencies in the 12 combinations of THC‐alcohol use (Section 3.3 and Figure 3) a statistically significant influence of the cannabis use on the extent of alcohol consumption can be concluded. Nevertheless, as the hair analysis cannot differentiate between substitutional (concurrent) and complementary (simultaneous) co‐use, a possible relationship in individual cases of the tested heterogenous group can have equalized the overall result.
3.5.2Relationship between use of alcohol and cocaine
In a meta‐analysis of the literature about the co‐use of cocaine and alcohol, Liu et al. found that the estimated prevalence of simultaneous use was 74% (95% confidence interval 50%–89%) and of concurrent use 77% (95% confidence interval 62%–87%). 3 For instance, in a study of Teodósio Valois‐Santos et al. in Brazil, 76.7% used crack combined with alcohol. 54 When both substances are simultaneously used, the amount of each substance consumed during a typical substance use episode was reported to increase significantly compared with when alcohol or cocaine are used alone. Particularly, cocaine powder users tended to use cocaine and alcohol concurrently and to take increased doses of both cocaine and alcohol when these were used in combination, whereas crack users tended to use alcohol at the end of crack‐using sessions. 55 , 56
Motivations for the simultaneous cocaine–alcohol use are the enhancement and prolongation of the euphorigenic effect, the alleviation of the acute unpleasant sequelae of cocaine subsequent to cocaine use such as dysphoria, paranoia, anxiety and fear, to be social, and to conform. 10 , 57 , 58 , 59 The combination of cocaine and alcohol induced a nonsignificant decrease in the subjective feelings of drunkenness, an increase in cocaine‐induced euphoria, and a significant improvement in alcohol‐related changes in psychomotor performance. 41 Alcohol significantly increases the systemic bioavailability of cocaine by a reduction in the amount of cocaine metabolized to benzoylecgonine and potentiates the neurochemical response to cocaine administration. 53 The prolongation is mainly explained by the formation of the active metabolite CE with about twice as long a half‐life compared with cocaine. 8 , 39 , 42 , 43
Negative consequences of the co‐use of cocaine and alcohol are the higher cardiotoxicity and increased risk of cardiac arrest, 60 greater facility to develop multiple and cross dependence and difficulties in adhering to and maintaining therapy, 9 , 61 and a possible potentiation of the tendency toward violent thoughts and threats, which may lead to an increase of violent behaviors. 59 However, there seems to be little evidence that cocaine alone or in combination with alcohol in itself induces profound violence, but that other contextual factors, like personality disorder or cocaine use disorder, may better explain the violence. 62
The comparison of cocaine and alcohol markers in hair in literature is confined to papers with the determination of CE. 33 , 34 , 63 , 64 , 65 Detection of CE proves simultaneous use of cocaine and alcohol and contradicts alleged abstinence from alcohol. It corroborates corresponding results from other alcohol markers. There was generally no unambiguous correlation between the concentrations of CE and EtG, 56 , 63 or fatty acid ethyl esters (FAEE) with EtPa as the most abundant ester. 64 , 65 There are several explanations for disagreeing results in COC‐positive hair samples. A high EtG or EtPa concentration without detection of CE could mean that alcohol and COC are not or only occasionally used together, or that COC results only from external contamination. On the other hand, a positive CE result despite negative EtG or EtPa can occur in cases of moderate alcohol use always combined with frequent cocaine use or if the illicit cocaine contained CE which is formed in certain manufacturing procedures with alcohol as the solvent. Furthermore, hair care and hair cosmetics may affect the markers to a different degree.
The results of the present study basically confirm this information from literature. From the 273 hair samples with cocaine ≥0.5 ng/mg, 153 (55.7%) exhibited alcohol markers in the ranges of social or abusive drinkers (Table 2), and CE was detected in 187 samples (68.5%). In 209 samples (76.6%), both EtG ≥ 5 pg/mg and CE ≥ 0.01 ng/mg or at least one of both were detected. This is in good agreement with the high prevalence of cocaine–alcohol co‐use and the preferred simultaneous use described in literature. Despite the large variation of the data, it follows from the statistical comparison of the cocaine concentrations (Section 3.2 and Figure 2) and the CE/COC ratios (Section 3.4 and Figure 5) between abstinence or moderate drinking, social drinking, and alcohol abuse, as well as from the sample frequencies in the 12 combinations of cocaine–alcohol use (Section 3.3 and Figure 4) that there is a tendency of increased consumption of both substances in co‐use in comparison to using only one of both.
3.6Limitations of the study
It is a limitation of this study that different hair lengths were used for the determination of drugs (0–6 cm or total length, if shorter) and alcohol markers (0–3 cm or total length, if shorter). However, as discussed in Section 3.1, this should have no basic effect on the comparison but may have contributed to the large variation seen in Figures 1 and 2.
As a further limitation, more than one drug was detected in 462 of the 918 drug‐positive samples (50.3%). This was neglected in the evaluation of the drug–alcohol relationships for single drugs but may have contributed essentially to the missing correlations, particularly for heroin, methadone, amphetamine, and ecstasy. In case of cocaine and THC, the separated evaluation of samples without further drugs basically confirmed the results obtained in the presence of additional other drugs.
In the group of low drug concentration, false positive results cannot completely be excluded in case of drug use by another family member. Finally, hair cosmetics is known to affect considerably the concentrations of both alcohol markers and drugs in hair. Dyeing or bleaching of hair within the last 6 months before sampling was reported, obvious from inspection of the hair or from the color of the extracts for 322 samples (24.5%). This, together with other variabilities in hair analysis, can have led to a misplacement of alcohol or drug consumption groups or alter the concentration distributions.
4CONCLUSIONS
It follows from the results that the evaluation of concentrations in hair is an appropriate way to study the extent of combined drug–alcohol consumption and complements other studies based on acquisition of consumption data by interview or questionnaire. Despite the limitations of the study, it is confirmed that combined use with alcohol has a high prevalence for all kinds of illicit drugs and must be taken into account in forensic and clinical interpretation. For THC, the extent of co‐abuse of alcohol appeared to be independent of the THC concentration in hair in the studied population. On the other hand, there is a clear tendency that for cocaine, the frequency and the extent of co‐abuse with alcohol increases with the severity of drug consumption. A larger number of samples would be necessary in order to obtain more conclusive conclusions about the relationship between use of heroin, methadone, amphetamine, or ecstasy and the extent of alcohol consumption.
CONFLICT OF INTEREST STATEMENT
The authors declare that they have no conflict of interest.
Supporting information
ACKNOWLEDGMENTS
The authors thank Mrs. Lena Westendorf and Dr. Maximilian Methling for experimental cooperation in the performance of hair analysis and the staff at the Offices of Social Services of the Hanseatic City of Bremen for the efficient cooperation in the realization of this project. Open Access funding enabled and organized by Projekt DEAL.