Cannabis is a widely consumed drug, so studying the effects of its chronic consumption becomes relevant. Regarding chronic consumption, the phenomenon of tolerance has been described in several drugs, including cannabis. Currently, multiple studies have addressed this phenomenon, with high heterogeneity in terms of methodology, evidence, and results. Our goal is to describe and analyze the literature on cannabis tolerance evaluated in physiological, cognitive, behavioral, and subjective responses, incorporating a critical perspective to account for some gaps and controversies in its study. Cannabis tolerance show a disparity between the effects produced after a first administration compared to its chronic use. Each of them incorporates heterogeneity of cannabinoids, doses, and routes of administration. Also, there is diversity in the regularity and temporal extension of consumption, as well as in its effects at the different response levels. Even when the heterogeneity of measurements allows for incorporating different perspectives, this results in poor standardization and a lack of rigor in what is understood as cannabis tolerance. Furthermore, there is no consideration of the stimuli present at drug administration, which have been relevant in the understanding of tolerance to other drugs as a learning process. Cannabis tolerance should be further studied, incorporating rigorous definitions and measurements that allow the phenomenon to be addressed in a global and standardized manner.

Motor neurons are highly dependent on membrane trafficking, in which the endoplasmic reticulum (ER) and its contact sites with endosomes, confer the ER the role of a long-distance communicator. Atlastin (Atl), a large GTPase located on the ER membrane is required for its function and its tubular structural dynamics. Atl also downregulates, by a yet unknown mechanism, the BMP (Bone Morphogenic Protein) pathway. In humans, Atl mutations are the second more common cause of Hereditary Spastic Paraplegia (HSP), a genetic disease characterized by spasticity of the lower extremities. Here, we explore the molecular basis of Atl-dependent defects on synaptic vesicle (SV) traffic in Drosophila under the hypothesis that those defects are the direct consequence of the atl -knock-down and not of the Atl-dependent BMP signaling upregulation. Motor neuronal knockdown of atl (Atl-KD) leads to an increase in synaptic and satellite bouton number similar to the increase in BMP signaling activity (TKV-CA). Neuronal Atl-KD also associates to a reduction in the boutons of the abundance of the SV markers CSP (Cysteine string protein) and VGLUT (vesicular glutamate transporter) as well as in TKV-CA larvae, both phenotypes are suppressed by decreasing the function of BMP receptor wishful thinking expressing one copy of the mutant receptor (wit /+). Surprisingly, we determined in Atl-KD larvae an increase in the CSP peripheral density and distribution, dependent on synaptic stimulation, that was not replicated in Tkv-CA larvae, suggesting that there could be differences in the mechanisms that underlie the reduction in CSP abundance. Additionally, we determined that Atl-KD associates to an increase in FM 1-43 unload but not in TKV-CA larvae. Moreover, one copy of w it was not able to suppress the FM-143 in Atl-KD larvae (Atl-KD, wit), supporting that BMP signaling does not participate in this phenotype. Together with the stimuli-dependent changes in the SV distribution and dynamics determined in Atl-KD larvae, we measured an increase in Rab11/CSP colocalization, suggesting changes in SV traffic through late recycling endosomes. Together our results suggest a mechanism by which the loss of an ER structuring protein in the motor neuron could, through its role in regulating SV and endosomal trafficking, explain defects in SV accumulation and synaptic dysfunction.

The relationship between people and their dogs can play a meaningful role in emotional support and psychological well-being, especially during university years. However, there are few validated instruments available for assessing the human–dog bond in Latin American populations. The present study sought to adapt and evaluate the Mexican version of the Monash Dog–Owner Relationship Scale (MDORS-M) for use with Chilean university students and also explore demographic and living arrangement factors associated with the strength of this relationship. A total of 312 undergraduate students who owned at least one dog participated in the study. The psychometric evaluation was conducted in two phases. First, the original 28-item MDORS-M was examined through exploratory factor analysis. Two items belonging to the Dog–Owner Interaction dimension showed substantial overlap with other factors and were therefore removed. A second exploratory factor analysis supported a revised 26-item version, referred to as the MDORS-CL26, which retained the scale’s three underlying dimensions: Dog–Owner Interaction, Emotional Closeness, and Perceived Costs. The resulting instrument showed strong reliability and internal consistency. Overall reliability indices were high (Cronbach’s α = 0.87; McDonald’s ω = 0.89), while reliability estimates for the individual subscales ranged from 0.77 to 0.90. Item-level analyses indicated that all remaining items contributed to their respective dimensions and should be retained. Confirmatory factor analysis provided support for the proposed three-factor structure, with all item–factor associations reaching statistical significance. Participants reported strong emotional connections with their dogs as more than nine out of ten students (92.3%) scored highly on Emotional Closeness, while nearly two-thirds (64.4%) reported moderate levels of Dog–Owner Interaction. In contrast, perceptions of the costs or burdens associated with dog ownership were comparatively low (56.1%). Female students tended to report stronger emotional bonds and more frequent interactions with their dogs than male students, although perceptions of cost of ownership were similar across groups. In addition, students whose dogs lived primarily indoors and those who shared the bedrooms, reported stronger and more positive relationship scores. The study contributes to the currently expanding body of anthrozoological research emerging from the Global South.

The regenerative potential of developing cortical axons depends on intrinsic mechanisms, such as axon-autonomous protein synthesis, that are still not fully understood. An emerging factor in this regenerative response is the bidirectional interplay between microtubule dynamics and the axonal ER. We hypothesize that locally synthesized ER proteins regulate microtubule dynamics and the regeneration of cortical axons. RNA data mining identified the ER-shaping protein Reticulon-1 as a relevant candidate across eight axonal transcriptomes. Using microfluidics, we show that axonal treatment with a small RNA against Reticulon-1 mRNA (Reticulon-1 knockdown) increases outgrowth of injured cortical axons while reducing their tubulin levels. We show by live-cell imaging that axonal Reticulon-1 knockdown increases microtubule growth rate in noninjured axons and restores this parameter after injury. Axonal inhibition of the microtubule-severing protein Spastin prevents the effects of Reticulon-1 knockdown over tubulin levels and outgrowth. We provide evidence that the Reticulon-1C isoform is synthesized within axons and attenuates Spastin-mediated microtubule severing. These findings support a model in which axonal protein synthesis regulates microtubule dynamics and axon outgrowth after injury.