Age differences in the behavioural economics of cannabis use: Do adolescents and adults differ on demand for cannabis and discounting of future reward?

BACKGROUND: Adolescence is a period of psychological and neural development in which harms associated with cannabis use may be heightened. We hypothesised that adolescent who use cannabis (adolescentsWUC) would have steeper delay discounting (preference for immediate over future rewards) and greater demand (relative valuation) for cannabis than adults who use cannabis (adultsWUC). METHODS: This cross-sectional study, part of the 'CannTeen' project, compared adultsWUC (n = 71, 26-29 years old) and adolescentsWUC (n = 76, 16-17 years old), and gender- and age-matched adolescent (n = 63) and adult (n = 64) controls. AdolescentsWUC and adultsWUC used cannabis 1-7 days/week and were matched on cannabis use frequency (4 days/week). The Monetary Choice Questionnaire assessed delay discounting. A modified Marijuana Purchase Task (MPT) assessed cannabis demand in adolescentsWUC and adultsWUC. The MPT yielded five indices: intensity (amount of cannabis used at zero cost), Omax (total peak expenditure), Pmax (price at peak expenditure), breakpoint (cost at which cannabis demand is suppressed to zero) and elasticity (degree to which cannabis use decreases with increasing price). Analyses were adjusted for covariates of gender, socioeconomic status, other illicit drug use. RESULTS: Both adolescentsWUC and adultsWUC had steeper delay discounting than controls (F, (1,254)= 9.13, p = 0.003, ηp2= 0.04), with no significant age effect or interaction. AdolescentsWUC showed higher intensity (F, (1,138)= 9.76, p = 0.002, ηp2= 0.07) and lower elasticity (F, (1,138)= 15.25, p < 0.001, ηp2= 0.10) than adultsWUC. There were no significant differences in Pmax, Omax or breakpoint. CONCLUSION: Individuals who use cannabis prefer immediate rewards more than controls. AdolescentsWUC, compared to adultsWUC, may be in a high-risk category with diminished sensitivity to cannabis price increases and a greater consumption of cannabis when it is free.

The CannTeen study: verbal episodic memory, spatial working memory, and response inhibition in adolescent and adult cannabis users and age-matched controls.

BACKGROUND: Preclinical and human studies suggest that adolescent cannabis use may be associated with worse cognitive outcomes than adult cannabis use. We investigated the associations between chronic cannabis use and cognitive function in adolescent and adult cannabis users and controls. We hypothesised user-status would be negatively associated with cognitive function and this relationship would be stronger in adolescents than adults. METHODS: As part of the 'CannTeen' project, this cross-sectional study assessed cognitive performance in adolescent cannabis users (n = 76; 16-17-year-olds), adolescent controls (n = 63), adult cannabis users (n = 71; 26-29-year-olds) and adult controls (n = 64). Users used cannabis 1-7 days/week. Adolescent and adult cannabis users were matched on cannabis use frequency (4 days/week) and time since last use (2.5 days). Verbal episodic memory (VEM) was assessed using the prose recall task, spatial working memory (SWM) was assessed using the spatial n-back task, and response inhibition was assessed with the stop-signal task. Primary outcome variables were: delayed recall, 3-back discriminability, and stop signal reaction time, respectively. RESULTS: Users had worse VEM than controls (F(1,268) = 7.423, p = 0.007). There were no significant differences between user-groups on SWM or response inhibition. Null differences were supported by Bayesian analyses. No significant interactions between age-group and user-group were found for VEM, SWM, or response inhibition. CONCLUSIONS: Consistent with previous research, there was an association between chronic cannabis use and poorer VEM, but chronic cannabis use was not associated with SWM or response inhibition. We did not find evidence for heightened adolescent vulnerability to cannabis-related cognitive impairment.

Effects of ecstasy on cooperative behaviour and perception of trustworthiness: a naturalistic study.

BACKGROUND: Acute recreational use of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') can promote pro-social effects which may alter interpersonal perceptions. AIMS: To explore such effects, this study investigated whether acute recreational use of ecstasy was associated with changes in individual perception of trustworthiness of people's faces and co-operative behaviours. METHOD: An independent group, repeated measures design was used in which 17 ecstasy users were tested on the night of drug use (day 0) and again three days later (day 3); 22 controls were tested on parallel days. On each day, participants rated the trustworthiness of 66 faces, carried out three co-operative behaviour tasks (public good; dictator; ultimatum game) and completed mood self-ratings. RESULTS: Acute ecstasy use was associated with increased face trustworthiness ratings and increased cooperative behaviour on the dictator and ultimatum games; on day 3 there were no group differences on any task. Self-ratings showed the standard acute ecstasy effects (euphoria, energy, jaw clenching) with negative effects (less empathy, compassion, more distrust, hostility) emerging on day 3. CONCLUSIONS: Our findings of increased perceived trustworthiness and co-operative behaviours following use of ecstasy suggest that a single dose of the drug enhances aspects of empathy. This may in turn contribute to its popularity as a recreational drug and potentially to its enhancement of the therapeutic alliance in psychotherapy.

The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories.

3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine-releaser that is widely used as a recreational drug. Preliminary work has supported the potential of MDMA in psychotherapy for post-traumatic stress disorder (PTSD). The neurobiological mechanisms underlying its putative efficacy are, however, poorly understood. Psychotherapy for PTSD usually requires that patients revisit traumatic memories, and it has been argued that this is easier to do under MDMA. Functional magnetic resonance imaging (fMRI) was used to investigate the effect of MDMA on recollection of favourite and worst autobiographical memories (AMs). Nineteen participants (five females) with previous experience with MDMA performed a blocked AM recollection (AMR) paradigm after ingestion of 100 mg of MDMA-HCl or ascorbic acid (placebo) in a double-blind, repeated-measures design. Memory cues describing participants' AMs were read by them in the scanner. Favourite memories were rated as significantly more vivid, emotionally intense and positive after MDMA than placebo and worst memories were rated as less negative. Functional MRI data from 17 participants showed robust activations to AMs in regions known to be involved in AMR. There was also a significant effect of memory valence: hippocampal regions showed preferential activations to favourite memories and executive regions to worst memories. MDMA augmented activations to favourite memories in the bilateral fusiform gyrus and somatosensory cortex and attenuated activations to worst memories in the left anterior temporal cortex. These findings are consistent with a positive emotional-bias likely mediated by MDMA's pro-monoaminergic pharmacology.

Sensitivity to optic flow in human cortical areas MT and MST.

The macaque V5/MT complex comprises several sub-regions but little is known of their human homologues. We examined human V5/MT with fMRI in terms of specificity to optic flow stimuli, a key characteristic of macaque MST. Stimuli were large fields of moving dots, forming coherent global flow patterns. Random motion was used as a control. Retinotopic mapping was also conducted. The previously suggested existence of at least two distinct sub-regions, MT and MST, within the V5/MT complex was confirmed. Human MT is activated about equally by all moving dot patterns, including random motion, suggesting that it has little sensitivity to global flow structure. As previously described, this region shows strong signs of retinotopic organization and is only weakly activated by stimuli confined to the ipsilateral hemifield. In human MST, located immediately anterior to MT and strongly driven by ipsilateral stimuli, activation varies markedly with optic flow structure. The strongest activation is produced by complex flow that contains multiple flow components (expansion, contraction and rotation). Single components produce rather less response, while rigid translation and random motion produce less still. The results suggest that human MST is strongly specialized for encoding global flow properties, while human MT is less so.

DNA template amplification genetic studies on archival human preimplantation biopsied microtubed cell samples.

Biopsied cell samples can remain in storage following an initial, unequivocally successful preimplantation genetic diagnosis (PGD). The fidelity of the DNA template for polymerase chain reaction (PCR) amplification of microtubed human preimplantation embryonic cells stored at -70 degrees C for extended periods of time (6 months to 4 years) has been assessed. PCR protocols and specific nested primer sets for the beta-globin, ZP3 and CA repeat motif successfully used for previous human embryo PGD research were employed for these studies. The results show that the DNA template of microtubed biopsied blastomere and mural trophectoderm cell samples stored for periods of up to 4 years may be successfully amplified by PCR. Specific gene sequences were able to be analysed at the 1-2 or 3-5 biopsied cell level with a 71-100% success rate. Analysis of DNA fragments amplified from the CA dinucleotide repeat locus showed that in 8/9 samples both alleles were amplified at the cellular level. No DNA contamination was detected in the stored microtubed samples, or in the experimental controls.

Archival fixed and analysed preimplantation human embryonic cells: a DNA resource for retrospective PCR analysis at the cellular level.

Biopsies of human embryonic cell preparations previously analysed by cytogenetic and/or fluorescent in-situ hybridization (FISH) chromosome probes provide a unique reference DNA resource for the archival preimplantation genetic diagnosis (PGD) of the transferred embryo. DNA polymerase chain reaction (PCR) may be utilized on these fixed cell preparations to verify equivocal FISH/PGD results. Retrospective PCR screens of the genotype of biopsied embryonic cell(s) may be of benefit in the case of a suspected genetic mutation. Currently, carrier detection or linkage analysis is often not possible because of early death of the fetus, or of patients with a lethal disease. Alternatively, fixed/stained 'failed fertilized' oocytes provide a resource to extend genetic analysis to infertile patients. A successful research is described which minimizes loss of individual analysed fixed/stained oocytes, metaphase chromosomes, and embryonic cell samples. Initial DNA amplification takes place in situ using a modified PCR protocol. Comparative cellular studies using primer sets previously used for PGD analyses show that 65% of the preparations amplified unequivocally using the modified protocol and primers for a CA repeat motif gene sequence, in comparison with 81% using the original PCR protocol. With further refinement and optimization, the methods outlined have the potential to retrospectively screen archival fixed chromosomes, gametes, and embryonic cells for clinical application, and enable the further study of the fixed human preimplantation embryo at the morphological, cell and molecular level.

Cytogenetic and fluorescent in-situ hybridization chromosomal studies on in-vitro fertilized and intracytoplasmic sperm injected 'failed-fertilized' human oocytes.

This study was undertaken to establish baseline data on the chromosomal status of 'failed-fertilized' oocytes derived from in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures. A cytogenetic analysis was undertaken on 162 IVF and 51 ICSI oocytes. In all, 82.1% (133/162) of the IVF and 78.4% (40/51) of the ICSI oocytes had metaphase II (MII) plates, of which 50.4% of the IVF and 47.5% of the ICSI oocytes were analysed further. Chromosomes of the G-group (21-22) were identified with the majority of the anomalies. No overall significant difference in the aneuploidy rate was found for the IVF (37.3%) of ICSI (31.6%) oocytes, or with maternal age. However, chromosome anomalies, e.g. diploidy, fragmented and broken chromatids, single sperm and oocyte chromatids, were found in oocytes from IVF patients aged > 36 years and in the ICSI oocytes throughout the maternal age range (31-38 years). The status of the polar body chromatin indicated that there was no overall significant difference in the maturation of the IVF and ICSI oocytes. Evidence of successful sperm delivery was found in 72.5% (37/51) of the ICSI failed-fertilized oocytes. In this group there was a significant increase in the incidence of premature chromosome condensation: 19.6% (10/51) contained sperm chromosomes, 7.8% (4/51) had swollen sperm heads, and the remaining 45.0% had condensed sperm heads. The presence of both sperm and MII oocyte chromosomes was found in 19.6% (10/51) of the ICSI and 8.6% (14/162) of the IVF failed-fertilized oocytes. Specific fluorescent in-situ hybridization DNA probes were used to re-analyse the chromosomes of karyotyped 'failed-fertilized' IVF oocytes and, for the first time, applied to the karyotyped chromosomes of failed-fertilized ICSI oocytes. The hybridization efficiency was 86-95% for the centromere probe and 100% for probes 21 and 18.

Biopulping process design and kinetics.

Biopulping is the solid-state fermentation of wood chips as a pretreatment for mechanical pulping processes. The two organisms that are currently of the greatest interest for biopulping are the white-rot fungi, Phanerochaete chrysosporium and Ceriporiopsis subvermispora. P. chrysosporium has been shown to successfully biopulp wood (33% energy savings; 39% improvement in tear index) without the need for sterilization of the wood or nutrient supplementation. Demonstrating the practical and economical feasibility of the biopulping process requires process modeling based on accurate kinetic data. Techniques to monitor dry weight loss and growth rate as functions of time using carbon dioxide production data have been developed. Growth was shown to be linear with time on unsupplemented chips and exponential with time on supplemented chips.